{"entity": "researcher", "timestamp": "2026-06-11T22:45:01.171Z", "family": "Zetterberg", "given": "Henrik", "initials": "H", "orcid": "0000-0003-3930-4354", "affiliations": [], "links": {"self": {"href": "https://publications.scilifelab.se/researcher/85efee74eb4a4b38b63cf2823d204529.json"}, "display": {"href": "https://publications.scilifelab.se/researcher/85efee74eb4a4b38b63cf2823d204529"}}, "publications": [{"entity": "publication", "iuid": "258c731df5164d1d8f4e7fde8d07f2df", "links": {"self": {"href": "https://publications.scilifelab.se/publication/258c731df5164d1d8f4e7fde8d07f2df.json"}, "display": {"href": "https://publications.scilifelab.se/publication/258c731df5164d1d8f4e7fde8d07f2df"}}, "title": "Phenotypic variability in early-onset dementia segregating with a novel APP (p.I718M) variant.", "authors": [{"family": "Johansson", "given": "Charlotte", "initials": "C"}, {"family": "Rodriguez-Vieitez", "given": "Elena", "initials": "E"}, {"family": "Bluma", "given": "Marina", "initials": "M"}, {"family": "Nennesmo", "given": "Inger", "initials": "I", "orcid": "0009-0000-0871-1147", "researcher": {"href": "https://publications.scilifelab.se/researcher/7422a07a064648a5a1dfed8a9889503b.json"}}, {"family": "Thonberg", "given": "H\u00e5kan", "initials": "H", "orcid": "0000-0003-4503-4717", "researcher": {"href": "https://publications.scilifelab.se/researcher/481958db26a2433ea8d5cc786c3b2bca.json"}}, {"family": "Ullgren", "given": "Abbe", "initials": "A"}, {"family": "Jelic", "given": "Vesna", "initials": "V"}, {"family": "Zetterberg", "given": "Henrik", "initials": "H", "orcid": "0000-0003-3930-4354", "researcher": {"href": "https://publications.scilifelab.se/researcher/85efee74eb4a4b38b63cf2823d204529.json"}}, {"family": "Blennow", "given": "Kaj", "initials": "K", "orcid": "0000-0002-1890-4193", "researcher": {"href": "https://publications.scilifelab.se/researcher/5e646be026ce42ecbfd4d62eca3f9bce.json"}}, {"family": "Nordberg", "given": "Agneta", "initials": "A"}, {"family": "Graff", "given": "Caroline", "initials": "C", "orcid": "0000-0002-9949-2951", "researcher": {"href": "https://publications.scilifelab.se/researcher/3faadb7b187046b090d947f85d8c4dd1.json"}}], "type": "journal article", "published": "2025-12-01", "journal": {"title": "Alzheimers Res Ther", "issn": "1758-9193", "volume": "17", "issue": "1", "pages": "254", "issn-l": null}, "abstract": "Autosomal dominant Alzheimer disease (ADAD) is caused by pathogenic variants in the APP, PSEN1 and PSEN2 genes, but a substantial fraction of reported variants is of unknown clinical significance. Here we report a novel variant in the amyloid precursor protein gene (APP p.I718M).\n\nFive siblings from a family with a multi-generational history of cognitive disease were assessed for cognitive impairment at the memory clinic at Karolinska University Hospital. Data were included for genetic analysis, segregation analysis, phenotyping and fluid biomarker analysis. Biomarker analyses were performed in CSF (A\u03b238, A\u03b240, A\u03b242, t-tau, p-tau181, NfL) and plasma (p-tau181, p-tau217, GFAP, NfL). CSF and plasma biomarkers were compared cross-sectionally to non-carrier controls or mutation carriers from other ADAD families. Also, amyloid PET, brain MRI and neuropathological data were included.\n\nThe siblings fulfilled criteria of probable AD (N = 4) or mixed AD and dementia with Lewy bodies (AD/DLB) (N = 1). Median age at onset was 53 years (range 47 to 67). The genetic variant, APP p.I718M, classified as likely pathogenic based on segregation analysis, population frequency and in silico prediction of pathogenicity, was detected in all five siblings. CSF A\u03b242/40 and A\u03b242/38 ratios were decreased, and the CSF A\u03b238/40 ratio was increased compared to controls. Additionally, elevated plasma concentrations of GFAP, NfL and p-tau181 were observed in APP p.I718M and other ADAD mutation carriers.\n\nThe APP p.I718M variant is associated with ADAD. Also, concomitant Lewy body pathology was observed in one sibling. The increase in CSF A\u03b238/40 suggests a shift in APP processing product-lines, but functional experiments are needed to characterize further cellular mechanisms of the APP p.I718M variant and to confirm its pathogenicity.\n\nThe online version contains supplementary material available at 10.1186/s13195-025-01890-9.", "doi": "10.1186/s13195-025-01890-9", "pmid": "41327373", "labels": {"NGI Uppsala (Uppsala Genome Center)": "Service", "National Genomics Infrastructure": "Service"}, "xrefs": [{"db": "pmc", "key": "PMC12670831"}, {"db": "pii", "key": "10.1186/s13195-025-01890-9"}], "notes": [], "created": "2025-12-10T11:59:20.425Z", "modified": "2025-12-21T19:09:30.938Z"}, {"entity": "publication", "iuid": "3b583a77d8b3461e8235d388087a4736", "links": {"self": {"href": "https://publications.scilifelab.se/publication/3b583a77d8b3461e8235d388087a4736.json"}, "display": {"href": "https://publications.scilifelab.se/publication/3b583a77d8b3461e8235d388087a4736"}}, "title": "Proteomic analysis of Down syndrome cerebrospinal fluid compared to late-onset and autosomal dominant Alzheimer\u00b4s disease.", "authors": [{"family": "Montoliu-Gaya", "given": "Laia", "initials": "L", "orcid": "0000-0001-7684-6318", "researcher": {"href": "https://publications.scilifelab.se/researcher/ddcfba9a14f14ba7ad912dcfd5fe92d9.json"}}, {"family": "Bian", "given": "Shijia", "initials": "S"}, {"family": "Dammer", "given": "Eric B", "initials": "EB", "orcid": "0000-0003-2947-7606", "researcher": {"href": "https://publications.scilifelab.se/researcher/026547f280c8451586bf92ab028090f7.json"}}, {"family": "Alcolea", "given": "Daniel", "initials": "D", "orcid": "0000-0002-3819-3245", "researcher": {"href": "https://publications.scilifelab.se/researcher/57c67b243f6a4ea38023ea8ae4f35e88.json"}}, {"family": "Sauer", "given": "Mathias", "initials": "M"}, {"family": "Mart\u00e1-Ariza", "given": "Mitchell", "initials": "M", "orcid": "0000-0002-2121-7685", "researcher": {"href": "https://publications.scilifelab.se/researcher/cbbcf516eead45b0999f29a79d94afe1.json"}}, {"family": "Ashton", "given": "Nicholas J", "initials": "NJ"}, {"family": "Belbin", "given": "Olivia", "initials": "O", "orcid": "0000-0002-6109-6371", "researcher": {"href": "https://publications.scilifelab.se/researcher/24e4b78f7fe8416596794fd2da2d3b4b.json"}}, {"family": "Fuchs", "given": "Johannes", "initials": "J", "orcid": "0000-0001-9317-6969", "researcher": {"href": "https://publications.scilifelab.se/researcher/65bf045dd14e45a4b61b4eb36e979bc0.json"}}, {"family": "Watson", "given": "Caroline M", "initials": "CM", "orcid": "0000-0001-6574-0833", "researcher": {"href": "https://publications.scilifelab.se/researcher/ab9107bdd4b246718df18654ffa1f67e.json"}}, {"family": "Ping", "given": "Lingyan", "initials": "L"}, {"family": "Duong", "given": "Duc M", "initials": "DM"}, {"family": "Nilsson", "given": "Johanna", "initials": "J", "orcid": "0000-0002-2856-6060", "researcher": {"href": "https://publications.scilifelab.se/researcher/fbfa9ce69cde46568cc315f0af089d2b.json"}}, {"family": "Barroeta", "given": "Isabel", "initials": "I"}, {"family": "Lantero-Rodriguez", "given": "Juan", "initials": "J", "orcid": "0000-0002-7426-678X", "researcher": {"href": "https://publications.scilifelab.se/researcher/492e19dc85914831bad0cefe5b7eb613.json"}}, {"family": "Videla", "given": "Laura", "initials": "L", "orcid": "0000-0002-9748-8465", "researcher": {"href": "https://publications.scilifelab.se/researcher/be25e716385448deb9741619b60b91bd.json"}}, {"family": "Benejam", "given": "Bessy", "initials": "B"}, {"family": "Roberts", "given": "Blaine R", "initials": "BR", "orcid": "0000-0001-5466-0053", "researcher": {"href": "https://publications.scilifelab.se/researcher/558f53068f1e45f1a828e9fcf8d905c6.json"}}, {"family": "Blennow", "given": "Kaj", "initials": "K", "orcid": "0000-0002-1890-4193", "researcher": {"href": "https://publications.scilifelab.se/researcher/5e646be026ce42ecbfd4d62eca3f9bce.json"}}, {"family": "Seyfried", "given": "Nicholas T", "initials": "NT", "orcid": "0000-0002-4507-624X", "researcher": {"href": "https://publications.scilifelab.se/researcher/9c940f8678724c38b1c6e98ea1b335e4.json"}}, {"family": "Levey", "given": "Allan I", "initials": "AI", "orcid": "0000-0002-3153-502X", "researcher": {"href": "https://publications.scilifelab.se/researcher/290c68791bfe4999b7a68ec208ea952b.json"}}, {"family": "Carmona-Iragui", "given": "Mar\u00eda", "initials": "M"}, {"family": "Gobom", "given": "Johan", "initials": "J", "orcid": "0000-0001-6193-6193", "researcher": {"href": "https://publications.scilifelab.se/researcher/add4c0c68cff447383c1f0184e2be943.json"}}, {"family": "Lle\u00f3", "given": "Alberto", "initials": "A", "orcid": "0000-0002-2568-5478", "researcher": {"href": "https://publications.scilifelab.se/researcher/0f93b0e1f2b0458ea41339b0935e892b.json"}}, {"family": "Wisniewski", "given": "Thomas", "initials": "T", "orcid": "0000-0002-3379-8966", "researcher": {"href": "https://publications.scilifelab.se/researcher/2c220af79d5a424f8bfe4e8d7c294276.json"}}, {"family": "Zetterberg", "given": "Henrik", "initials": "H", "orcid": "0000-0003-3930-4354", "researcher": {"href": "https://publications.scilifelab.se/researcher/85efee74eb4a4b38b63cf2823d204529.json"}}, {"family": "Fortea", "given": "Juan", "initials": "J", "orcid": "0000-0002-1340-638X", "researcher": {"href": "https://publications.scilifelab.se/researcher/339f94b3044b4d8b82167c6968085be2.json"}}, {"family": "Johnson", "given": "Erik C B", "initials": "ECB", "orcid": "0000-0002-0604-2944", "researcher": {"href": "https://publications.scilifelab.se/researcher/9e9903bd257a439b9a8072f0d478a558.json"}}], "type": "journal article", "published": "2025-07-01", "journal": {"title": "Nat Commun", "issn": "2041-1723", "volume": "16", "issue": "1", "pages": "6003", "issn-l": "2041-1723"}, "abstract": "Almost all individuals with Down Syndrome (DS) develop Alzheimer's disease (AD) by mid to late life. However, the degree to which AD in DS shares pathological changes with sporadic late-onset AD (LOAD) and autosomal dominant AD (ADAD) beyond core AD biomarkers such as amyloid-\u03b2 (A\u03b2) and tau is unknown. Here, we used proteomics of cerebrospinal fluid from individuals with DS (n = 229) in the Down Alzheimer Barcelona Neuroimaging Initiative (DABNI) cohort to assess the evolution of AD pathophysiology from asymptomatic to dementia stages and compared the proteomic biomarker changes in DS to those observed in LOAD and ADAD. Although many proteomic alterations were shared across DS, LOAD, and ADAD, DS demonstrated more severe changes in immune-related proteins, extracellular matrix pathways, and plasma proteins likely related to blood-brain barrier dysfunction compared to LOAD. These changes were present in young adults with DS prior to the onset of A\u03b2 or tau pathology, suggesting they are associated with trisomy 21 and may serve as risk factors for DSAD. DSAD showed an earlier increase in markers of axonal and white matter pathology and earlier changes in markers potentially associated with cerebral amyloid angiopathy compared to ADAD. The unique features of DSAD may have important implications for treatment strategies in this population.", "doi": "10.1038/s41467-025-61054-z", "pmid": "40595720", "labels": {"Glycoproteomics and MS Proteomics": "Collaborative"}, "xrefs": [{"db": "pmc", "key": "PMC12214755"}, {"db": "pii", "key": "10.1038/s41467-025-61054-z"}], "notes": [], "created": "2025-10-23T13:09:26.368Z", "modified": "2025-10-23T13:09:27.449Z"}, {"entity": "publication", "iuid": "b6f2c0aa24c44d3a899a4f6703ca28f1", "links": {"self": {"href": "https://publications.scilifelab.se/publication/b6f2c0aa24c44d3a899a4f6703ca28f1.json"}, "display": {"href": "https://publications.scilifelab.se/publication/b6f2c0aa24c44d3a899a4f6703ca28f1"}}, "title": "Plasma brain-derived tau correlates with cerebral infarct volume.", "authors": [{"family": "Gonzalez-Ortiz", "given": "Fernando", "initials": "F", "orcid": "0000-0001-7897-9456", "researcher": {"href": "https://publications.scilifelab.se/researcher/c4bc7b2303004dcc81fe355d7c15bb4c.json"}}, {"family": "Holmegaard", "given": "Lukas", "initials": "L"}, {"family": "Andersson", "given": "Bj\u00f6rn", "initials": "B"}, {"family": "Br\u00e4nnmark", "given": "Cecilia", "initials": "C"}, {"family": "Blomstrand", "given": "Christian", "initials": "C"}, {"family": "Zetterberg", "given": "Henrik", "initials": "H", "orcid": "0000-0003-3930-4354", "researcher": {"href": "https://publications.scilifelab.se/researcher/85efee74eb4a4b38b63cf2823d204529.json"}}, {"family": "Jood", "given": "Katarina", "initials": "K", "orcid": "0000-0001-8746-1771", "researcher": {"href": "https://publications.scilifelab.se/researcher/0d671938a5264a569660e88b00fde93d.json"}}, {"family": "Blennow", "given": "Kaj", "initials": "K", "orcid": "0000-0002-1890-4193", "researcher": {"href": "https://publications.scilifelab.se/researcher/5e646be026ce42ecbfd4d62eca3f9bce.json"}}, {"family": "Jern", "given": "Christina", "initials": "C", "orcid": "0000-0002-7531-2354", "researcher": {"href": "https://publications.scilifelab.se/researcher/13e58d6c4a2e44cd9067f38a2ff2ea32.json"}}, {"family": "Stanne", "given": "Tara M", "initials": "TM", "orcid": "0000-0001-9668-0407", "researcher": {"href": "https://publications.scilifelab.se/researcher/f3c967b386124a3199b2373de1111d03.json"}}], "type": "journal article", "published": "2025-02-00", "journal": {"title": "J. Intern. Med.", "issn": "1365-2796", "volume": "297", "issue": "2", "pages": "173-185", "issn-l": "0954-6820"}, "abstract": "A blood-based biomarker that accurately reflects neuronal injury in acute ischemic stroke could be an easily accessible and cost-effective complement to clinical and radiological evaluation. Here, we investigate whether plasma levels of the novel biomarker brain-derived tau (BD-tau) reflect cerebral infarct volumes and whether BD-tau can improve clinical outcome prediction.\n\nThe present study included 713 consecutive cases from two different hospital-based cohorts, the Sahlgrenska Academy Study on Ischemic Stroke (SAHLSIS) and SAHLSIS phase 2 (SAHLSIS2). Acute stroke severity was determined by the Scandinavian Stroke Scale converted to the National Institutes of Health stroke scale (NIHSS) in SAHLSIS and by the NIHSS in SAHLSIS2. All participants were assessed for functional outcome 3 months after stroke by the modified Rankin Scale, and 254 participants in SAHLSIS had quantitative neuroimaging available.\n\nPlasma BD-tau concentrations and cerebral infarct volumes were highly correlated (\u03c1 0.72, p < 0.001). BD-tau improved the prognostic accuracy of suffering an unfavorable outcome over age and stroke severity in the whole cohort. However, the gain in predictive power was dependent on stroke severity and infarct location. The largest improvement was observed for mild ischemic strokes (NIHSS <5; area under the curve [AUC] = 0.73 for age + NIHSS versus AUC = 0.84 with addition of BD-tau; DeLong p 0.02), posterior circulation stroke (AUC = 0.75 vs. AUC = 0.84; DeLong p 0.06) and more specifically for infarcts in the brainstem/cerebellum (AUC = 0.74 vs. 0.87; DeLong p 0.009).\n\nPlasma BD-tau can provide information on the extent of acute neuronal damage in ischemic stroke and adds prognostic value for outcome, especially for mild and posterior circulation strokes.", "doi": "10.1111/joim.20041", "pmid": "39639627", "labels": {"Clinical Genomics": "Collaborative", "Clinical Genomics Gothenburg": "Collaborative"}, "xrefs": [{"db": "pmc", "key": "PMC11771704"}], "notes": [], "created": "2025-07-08T13:54:34.800Z", "modified": "2025-07-08T13:54:35.034Z"}, {"entity": "publication", "iuid": "ce7ad1afa4874fc6bb73127f9cefddc0", "links": {"self": {"href": "https://publications.scilifelab.se/publication/ce7ad1afa4874fc6bb73127f9cefddc0.json"}, "display": {"href": "https://publications.scilifelab.se/publication/ce7ad1afa4874fc6bb73127f9cefddc0"}}, "title": "Phospho-tau serine-262 and serine-356 as biomarkers of pre-tangle soluble tau assemblies in Alzheimer's disease.", "authors": [{"family": "Islam", "given": "Tohidul", "initials": "T", "orcid": "0000-0003-1561-944X", "researcher": {"href": "https://publications.scilifelab.se/researcher/a0693554436c4017a605281f3d97d373.json"}}, {"family": "Hill", "given": "Emily", "initials": "E"}, {"family": "Abrahamson", "given": "Eric E", "initials": "EE"}, {"family": "Servaes", "given": "Stijn", "initials": "S"}, {"family": "Smirnov", "given": "Denis S", "initials": "DS"}, {"family": "Zeng", "given": "Xuemei", "initials": "X"}, {"family": "Sehrawat", "given": "Anuradha", "initials": "A"}, {"family": "Chen", "given": "Yijun", "initials": "Y", "orcid": "0009-0001-4579-4057", "researcher": {"href": "https://publications.scilifelab.se/researcher/0e7eb6e67f694af8b1dfb26c4dbcf97c.json"}}, {"family": "Kac", "given": "Przemys\u0142aw R", "initials": "PR", "orcid": "0000-0001-5083-0924", "researcher": {"href": "https://publications.scilifelab.se/researcher/d7d23b25a3774bb696abf5522147d249.json"}}, {"family": "Kvartsberg", "given": "Hlin", "initials": "H", "orcid": "0000-0002-4481-508X", "researcher": {"href": "https://publications.scilifelab.se/researcher/be021173500e46a59ec36f4b34ee607f.json"}}, {"family": "Olsson", "given": "Maria", "initials": "M"}, {"family": "Sjons", "given": "Emma", "initials": "E", "orcid": "0009-0008-5030-114X", "researcher": {"href": "https://publications.scilifelab.se/researcher/da9154ad214441e3adc4a094c7c73e32.json"}}, {"family": "Gonzalez-Ortiz", "given": "Fernando", "initials": "F", "orcid": "0000-0001-7897-9456", "researcher": {"href": "https://publications.scilifelab.se/researcher/c4bc7b2303004dcc81fe355d7c15bb4c.json"}}, {"family": "Therriault", "given": "Joseph", "initials": "J"}, {"family": "Tissot", "given": "C\u00e9cile", "initials": "C", "orcid": "0000-0003-2711-3833", "researcher": {"href": "https://publications.scilifelab.se/researcher/bbdaa319e358466696ff529d1221591d.json"}}, {"family": "Del Popolo", "given": "Ivana", "initials": "I", "orcid": "0009-0005-6480-4117", "researcher": {"href": "https://publications.scilifelab.se/researcher/2bd3286ad15640dcb5358891c82d0c7a.json"}}, {"family": "Rahmouni", "given": "Nesrine", "initials": "N"}, {"family": "Richardson", "given": "Abbie", "initials": "A"}, {"family": "Mitchell", "given": "Victoria", "initials": "V"}, {"family": "Zetterberg", "given": "Henrik", "initials": "H", "orcid": "0000-0003-3930-4354", "researcher": {"href": "https://publications.scilifelab.se/researcher/85efee74eb4a4b38b63cf2823d204529.json"}}, {"family": "Pascoal", "given": "Tharick A", "initials": "TA", "orcid": "0000-0001-9057-8014", "researcher": {"href": "https://publications.scilifelab.se/researcher/2bfa45d39b324b2ab78c12ec044ebe48.json"}}, {"family": "Lashley", "given": "Tammaryn", "initials": "T", "orcid": "0000-0001-7389-0348", "researcher": {"href": "https://publications.scilifelab.se/researcher/533fe74a716840b2a55fddf0452f2a23.json"}}, {"family": "Wall", "given": "Mark J", "initials": "MJ"}, {"family": "Galasko", "given": "Douglas", "initials": "D"}, {"family": "Rosa-Neto", "given": "Pedro", "initials": "P", "orcid": "0000-0001-9116-1376", "researcher": {"href": "https://publications.scilifelab.se/researcher/2a2e4f85e17f45489cde7f8d8430daa4.json"}}, {"family": "Ikonomovic", "given": "Milos D", "initials": "MD"}, {"family": "Blennow", "given": "Kaj", "initials": "K", "orcid": "0000-0002-1890-4193", "researcher": {"href": "https://publications.scilifelab.se/researcher/5e646be026ce42ecbfd4d62eca3f9bce.json"}}, {"family": "Karikari", "given": "Thomas K", "initials": "TK", "orcid": "0000-0003-1422-4358", "researcher": {"href": "https://publications.scilifelab.se/researcher/cf3831a3e6a341f4b0a728e591de5b42.json"}}], "type": "journal article", "published": "2025-02-00", "journal": {"title": "Nat. Med.", "issn": "1546-170X", "volume": "31", "issue": "2", "pages": "574-588", "issn-l": "1078-8956"}, "abstract": "Patients with Alzheimer's disease (AD) with little or no quantifiable insoluble brain tau neurofibrillary tangle (NFT) pathology demonstrate stronger clinical benefits of therapies than those with advanced NFTs. The formation of NFTs can be prevented by targeting the intermediate soluble tau assemblies (STAs). However, biochemical understanding and biomarkers of STAs are lacking. We show that Tris-buffered saline-soluble tau aggregates from autopsy-verified AD brain tissues include the core sequence ~tau258-368. In neuropathological assessments, antibodies against the phosphorylation sites serine-262 and serine-356 within the STA core almost exclusively stained granular (that is, prefibrillar) tau aggregates in pre-NFTs while antibodies against phosphorylation at serine-202 and threonine-205 and threonine-231, outside the STA core, stained the entire spectrum of tau aggregates in pre-NFTs and mature NFTs, dystrophic neurites and neuropil threads in the hippocampus. Functionally, a recombinantly produced STA core peptide robustly altered neuronal excitability and synaptic transmission in mouse hippocampal brain slices. Furthermore, we developed a cerebrospinal fluid assay that differentiated STAs in AD from non-AD tauopathies, correlated with the severity of NFT burden and cognitive decline independently of amyloid beta deposition, and with tau positron emission tomography uptake across Braak NFT stages. Together, our findings inform about the status of early-stage tau aggregation, reveal aggregation-relevant phosphorylation epitopes in tau and offer a diagnostic biomarker and targeted therapeutic opportunities for AD.", "doi": "10.1038/s41591-024-03400-0", "pmid": "39930142", "labels": {"Integrated Microscopy Technologies Gothenburg": "Service"}, "xrefs": [{"db": "pmc", "key": "PMC11835754"}, {"db": "pii", "key": "10.1038/s41591-024-03400-0"}], "notes": [], "created": "2025-11-05T13:53:57.536Z", "modified": "2025-11-05T13:53:58.203Z"}, {"entity": "publication", "iuid": "4deb438b26af4bddbf57dee49f870159", "links": {"self": {"href": "https://publications.scilifelab.se/publication/4deb438b26af4bddbf57dee49f870159.json"}, "display": {"href": "https://publications.scilifelab.se/publication/4deb438b26af4bddbf57dee49f870159"}}, "title": "Chemical signatures delineate heterogeneous amyloid plaque populations across the Alzheimer's disease spectrum.", "authors": [{"family": "Koutarapu", "given": "Srinivas", "initials": "S", "orcid": "0000-0002-4355-6733", "researcher": {"href": "https://publications.scilifelab.se/researcher/79cb4df7812041b8ad57fbdd6bc42f01.json"}}, {"family": "Ge", "given": "Junyue", "initials": "J"}, {"family": "Dulewicz", "given": "Maciej", "initials": "M"}, {"family": "Srikrishna", "given": "Meera", "initials": "M"}, {"family": "Szadziewska", "given": "Alicja", "initials": "A"}, {"family": "Wood", "given": "Jack", "initials": "J"}, {"family": "Blennow", "given": "Kaj", "initials": "K"}, {"family": "Zetterberg", "given": "Henrik", "initials": "H", "orcid": "0000-0003-3930-4354", "researcher": {"href": "https://publications.scilifelab.se/researcher/85efee74eb4a4b38b63cf2823d204529.json"}}, {"family": "Michno", "given": "Wojciech", "initials": "W", "orcid": "0000-0002-3096-3604", "researcher": {"href": "https://publications.scilifelab.se/researcher/7b4307eb6e45426e8176337e88c9c344.json"}}, {"family": "Ryan", "given": "Natalie S", "initials": "NS"}, {"family": "Lashley", "given": "Tammaryn", "initials": "T"}, {"family": "Savas", "given": "Jeffrey", "initials": "J"}, {"family": "Sch\u00f6ll", "given": "Michael", "initials": "M", "orcid": "0000-0001-7800-1781", "researcher": {"href": "https://publications.scilifelab.se/researcher/2332043f0c4142309890b37050498c0c.json"}}, {"family": "Hanrieder", "given": "J\u00f6rg", "initials": "J", "orcid": "0000-0001-6059-198X", "researcher": {"href": "https://publications.scilifelab.se/researcher/4e65454100674f98bf8f2575093f2441.json"}}], "type": "journal article", "published": "2024-06-03", "journal": {"title": "bioRxiv", "issn": "2692-8205", "issn-l": null}, "abstract": "Amyloid plaque deposition is recognized as the primary pathological hallmark of Alzheimer's disease(AD) that precedes other pathological events and cognitive symptoms. Plaque pathology represents itself with an immense polymorphic variety comprising plaques with different stages of amyloid fibrillization ranging from diffuse to fibrillar, mature plaques. The association of polymorphic A\u03b2 plaque pathology with AD pathogenesis, clinical symptoms and disease progression remains unclear. Advanced chemical imaging tools, such as functional amyloid microscopy combined with MALDI mass spectrometry imaging (MSI), are now enhanced by deep learning algorithms. This integration allows for precise delineation of polymorphic plaque structures and detailed identification of their associated A\u03b2 compositions. We here set out to make use of these tools to interrogate heterogenic plaque types and their associated biochemical architecture. Our findings reveal distinct A\u03b2 signatures that differentiate diffuse plaques from fibrilized ones, with the latter showing substantially higher levels of A\u03b2x-40. Notably, within the fibrilized category, we identified a distinct subtype known as coarse-grain plaques. Both in sAD and fAD brain tissue, coarse grain plaques contained more A\u03b2x-40 and less A\u03b2x-42 compared with cored plaques. The coarse grain plaques in both sAD and fAD also showed higher levels of neuritic content including paired helical filaments (PHF-1)/phosphorylated phospho Tau-immunopositive neurites. Finally, the A\u03b2 peptide content in coarse grain plaques resembled that of vascular A\u03b2 deposits (CAA) though with relatively higher levels of A\u03b21-42 and pyroglutamated A\u03b2x-40 and A\u03b2x-42 species in coarse grain plaques. This is the first of its kind study on spatial in situ biochemical characterization of different plaque morphotypes demonstrating the potential of the correlative imaging techniques used that further increase the understanding of heterogeneous AD pathology. Linking the biochemical characteristics of amyloid plaque polymorphisms with various AD etiologies and toxicity mechanisms is crucial. Understanding the connection between plaque structure and disease pathogenesis can enhance our insights. This knowledge is particularly valuable for developing and advancing novel, amyloid-targeting therapeutics.", "doi": "10.1101/2024.06.03.596890", "pmid": "38895368", "labels": {"Integrated Microscopy Technologies Gothenburg": "Service"}, "xrefs": [{"db": "pmc", "key": "PMC11185524"}, {"db": "pii", "key": "2024.06.03.596890"}], "notes": [], "created": "2024-11-15T12:07:53.119Z", "modified": "2024-11-15T12:07:54.065Z"}, {"entity": "publication", "iuid": "57e0117b46834ba4be1ceefa899cd14b", "links": {"self": {"href": "https://publications.scilifelab.se/publication/57e0117b46834ba4be1ceefa899cd14b.json"}, "display": {"href": "https://publications.scilifelab.se/publication/57e0117b46834ba4be1ceefa899cd14b"}}, "title": "APP-BACE1 Interaction and Intracellular Localization Regulate A\u03b2 Production in iPSC-Derived Cortical Neurons.", "authors": [{"family": "Roselli", "given": "Sandra", "initials": "S", "orcid": "0000-0003-2998-3760", "researcher": {"href": "https://publications.scilifelab.se/researcher/967692ca9b2e43078b0f732e08133f0c.json"}}, {"family": "Satir", "given": "Tugce Munise", "initials": "TM", "orcid": "0000-0001-9021-1650", "researcher": {"href": "https://publications.scilifelab.se/researcher/ae8aad9da4a241e5b8fbfe9a9bc57624.json"}}, {"family": "Camacho", "given": "Rafael", "initials": "R", "orcid": "0000-0003-2325-6407", "researcher": {"href": "https://publications.scilifelab.se/researcher/6a7a8cfe28634821984b078ce3246343.json"}}, {"family": "Fruhw\u00fcrth", "given": "Stefanie", "initials": "S", "orcid": "0000-0003-4035-7330", "researcher": {"href": "https://publications.scilifelab.se/researcher/ed598b441d80455db788599f7cb307e9.json"}}, {"family": "Bergstr\u00f6m", "given": "Petra", "initials": "P", "orcid": "0000-0003-1803-165X", "researcher": {"href": "https://publications.scilifelab.se/researcher/2c7a0d0f6ee448e281dab1d9abf4f80c.json"}}, {"family": "Zetterberg", "given": "Henrik", "initials": "H", "orcid": "0000-0003-3930-4354", "researcher": {"href": "https://publications.scilifelab.se/researcher/85efee74eb4a4b38b63cf2823d204529.json"}}, {"family": "Agholme", "given": "Lotta", "initials": "L", "orcid": "0000-0003-3816-7474", "researcher": {"href": "https://publications.scilifelab.se/researcher/a7034ae6b9644a6fabd3bfb6d719459b.json"}}], "type": "journal article", "published": "2023-10-00", "journal": {"title": "Cell Mol Neurobiol", "issn": "1573-6830", "volume": "43", "issue": "7", "pages": "3653-3668", "issn-l": null}, "abstract": "Alzheimer's disease (AD) is characterized pathologically by amyloid \u03b2 (A\u03b2)-containing plaques. Generation of A\u03b2 from amyloid precursor protein (APP) by two enzymes, \u03b2- and \u03b3-secretase, has therefore been in the AD research spotlight for decades. Despite this, how the physical interaction of APP with the secretases influences APP processing is not fully understood. Herein, we compared two genetically identical human iPSC-derived neuronal cell types: low A\u03b2-secreting neuroprogenitor cells (NPCs) and high A\u03b2-secreting mature neurons, as models of low versus high A\u03b2 production. We investigated levels of substrate, enzymes and products of APP amyloidogenic processing and correlated them with the proximity of APP to \u03b2- and \u03b3-secretase in endo-lysosomal organelles. In mature neurons, increased colocalization of full-length APP with the \u03b2-secretase BACE1 correlated with increased \u03b2-cleavage product sAPP\u03b2. Increased flAPP/BACE1 colocalization was mainly found in early endosomes. In the same way, increased colocalization of APP-derived C-terminal fragment (CTF) with presenilin-1 (PSEN1), the catalytic subunit of \u03b3-secretase, was seen in neurons as compared to NPCs. Furthermore, most of the interaction of APP with BACE1 in low A\u03b2-secreting NPCs seemed to derive from CTF, the remaining APP part after BACE1 cleavage, indicating a possible novel product-enzyme inhibition. In conclusion, our results suggest that interaction of APP and APP cleavage products with their secretases can regulate A\u03b2 production both positively and negatively. \u03b2- and \u03b3-Secretases are difficult targets for AD treatment due to their ubiquitous nature and wide range of substrates. Therefore, targeting APP-secretase interactions could be a novel treatment strategy for AD. Colocalization of APP species with BACE1 in a novel model of low- versus high-A\u03b2 secretion-Two genetically identical human iPSC-derived neuronal cell types: low A\u03b2-secreting neuroprogenitor cells (NPCs) and high A\u03b2 secreting mature neurons, were compared. Increased full-length APP (flAPP)/BACE1 colocalization in early endosomes was seen in neurons, while APP-CTF/BACE1 colocalization was much higher than flAPP/BACE1 colocalization in NPCs, although the cellular location was not determined.", "doi": "10.1007/s10571-023-01374-0", "pmid": "37355492", "labels": {"Integrated Microscopy Technologies Gothenburg": "Service"}, "xrefs": [{"db": "pmc", "key": "PMC10477112"}, {"db": "pii", "key": "10.1007/s10571-023-01374-0"}], "notes": [], "created": "2023-12-01T10:50:59.915Z", "modified": "2023-12-01T10:51:00.090Z"}, {"entity": "publication", "iuid": "7ea962d923e7411b84994b78d79378f9", "links": {"self": {"href": "https://publications.scilifelab.se/publication/7ea962d923e7411b84994b78d79378f9.json"}, "display": {"href": "https://publications.scilifelab.se/publication/7ea962d923e7411b84994b78d79378f9"}}, "title": "Correlative Chemical Imaging Identifies Amyloid Peptide Signatures of Neuritic Plaques and Dystrophy in Human Sporadic Alzheimer's Disease.", "authors": [{"family": "Koutarapu", "given": "Srinivas", "initials": "S"}, {"family": "Ge", "given": "Junyue", "initials": "J"}, {"family": "Jha", "given": "Durga", "initials": "D"}, {"family": "Blennow", "given": "Kaj", "initials": "K"}, {"family": "Zetterberg", "given": "Henrik", "initials": "H", "orcid": "0000-0003-3930-4354", "researcher": {"href": "https://publications.scilifelab.se/researcher/85efee74eb4a4b38b63cf2823d204529.json"}}, {"family": "Lashley", "given": "Tammaryn", "initials": "T"}, {"family": "Michno", "given": "Wojciech", "initials": "W", "orcid": "0000-0002-3096-3604", "researcher": {"href": "https://publications.scilifelab.se/researcher/7b4307eb6e45426e8176337e88c9c344.json"}}, {"family": "Hanrieder", "given": "J\u00f6rg", "initials": "J", "orcid": "0000-0001-6059-198X", "researcher": {"href": "https://publications.scilifelab.se/researcher/4e65454100674f98bf8f2575093f2441.json"}}], "type": "journal article", "published": "2023-06-00", "journal": {"title": "Brain Connect", "issn": "2158-0022", "volume": "13", "issue": "5", "pages": "297-306", "issn-l": null}, "abstract": "Alzheimer's disease (AD) is the most common neurodegenerative disease. The predominantly sporadic form of AD is age-related, but the underlying pathogenic mechanisms remain not fully understood. Current efforts to combat the disease focus on the main pathological hallmarks, in particular beta-amyloid (A\u03b2) plaque pathology. According to the amyloid cascade hypothesis, A\u03b2 is the critical early initiator of AD pathogenesis. Plaque pathology is very heterogeneous, where a subset of plaques, neuritic plaques (NPs), are considered most neurotoxic rendering their in-depth characterization essential to understand A\u03b2 pathogenicity. Objective: To delineate the chemical traits specific to NP types, we investigated senile A\u03b2 pathology in the postmortem, human sporadic AD brain using advanced correlative biochemical imaging based on immunofluorescence (IF) microscopy and mass spectrometry imaging (MSI). Methods: Immunostaining-guided MSI identified distinct A\u03b2 signatures of NPs characterized by increased A\u03b21-42(ox) and A\u03b22-42. Moreover, correlation with a marker of dystrophy (reticulon 3 [RTN3]) identified key A\u03b2 species that both delineate NPs and display association with neuritic dystrophy. Results: Together, these correlative imaging data shed light on the complex biochemical architecture of NPs and associated dystrophic neurites. These in turn are obvious targets for disease-modifying treatment strategies, as well as novel biomarkers of A\u03b2 pathogenicity.Conclusion:", "doi": "10.1089/brain.2022.0047", "pmid": "36074939", "labels": {"Integrated Microscopy Technologies Gothenburg": "Service"}, "xrefs": [{"db": "pmc", "key": "PMC10398722"}], "notes": [], "created": "2023-02-16T08:26:30.200Z", "modified": "2023-12-01T10:46:54.067Z"}, {"entity": "publication", "iuid": "4a43a31c1f84404bb148ab52b6c5148e", "links": {"self": {"href": "https://publications.scilifelab.se/publication/4a43a31c1f84404bb148ab52b6c5148e.json"}, "display": {"href": "https://publications.scilifelab.se/publication/4a43a31c1f84404bb148ab52b6c5148e"}}, "title": "Chemical traits of cerebral amyloid angiopathy in familial British-, Danish-, and non-Alzheimer's dementias.", "authors": [{"family": "Michno", "given": "Wojciech", "initials": "W", "orcid": "0000-0002-3096-3604", "researcher": {"href": "https://publications.scilifelab.se/researcher/7b4307eb6e45426e8176337e88c9c344.json"}}, {"family": "Koutarapu", "given": "Srinivas", "initials": "S"}, {"family": "Camacho", "given": "Rafael", "initials": "R", "orcid": "0000-0003-2325-6407", "researcher": {"href": "https://publications.scilifelab.se/researcher/6a7a8cfe28634821984b078ce3246343.json"}}, {"family": "Toomey", "given": "Christina", "initials": "C"}, {"family": "Stringer", "given": "Katie", "initials": "K"}, {"family": "Minta", "given": "Karolina", "initials": "K"}, {"family": "Ge", "given": "Junyue", "initials": "J"}, {"family": "Jha", "given": "Durga", "initials": "D"}, {"family": "Fernandez-Rodriguez", "given": "Julia", "initials": "J"}, {"family": "Brinkmalm", "given": "Gunnar", "initials": "G"}, {"family": "Zetterberg", "given": "Henrik", "initials": "H", "orcid": "0000-0003-3930-4354", "researcher": {"href": "https://publications.scilifelab.se/researcher/85efee74eb4a4b38b63cf2823d204529.json"}}, {"family": "Blennow", "given": "Kaj", "initials": "K"}, {"family": "Ryan", "given": "Natalie S", "initials": "NS"}, {"family": "Lashley", "given": "Tammaryn", "initials": "T"}, {"family": "Hanrieder", "given": "J\u00f6rg", "initials": "J", "orcid": "0000-0001-6059-198X", "researcher": {"href": "https://publications.scilifelab.se/researcher/4e65454100674f98bf8f2575093f2441.json"}}], "type": "journal article", "published": "2022-11-00", "journal": {"title": "J. Neurochem.", "issn": "1471-4159", "volume": "163", "issue": "3", "pages": "233-246", "issn-l": "0022-3042"}, "abstract": "Familial British dementia (FBD) and familial Danish dementia (FDD) are autosomal dominant forms of dementia caused by mutations in the integral membrane protein 2B (ITM2B, also known as BRI2) gene. Secretase processing of mutant BRI2 leads to secretion and deposition of BRI2-derived amyloidogenic peptides, ABri and ADan that resemble APP/\u03b2-amyloid (A\u03b2) pathology, which is characteristic of Alzheimer's disease (AD). Amyloid pathology in FBD/FDD manifests itself predominantly in the microvasculature by ABri/ADan containing cerebral amyloid angiopathy (CAA). While ABri and ADan peptide sequences differ only in a few C-terminal amino acids, CAA in FDD is characterized by co-aggregation of ADan with A\u03b2, while in contrast no A\u03b2 deposition is observed in FBD. The fact that FDD patients display an earlier and more severe disease onset than FBD suggests a potential role of ADan and A\u03b2 co-aggregation that promotes a more rapid disease progression in FDD compared to FBD. It is therefore critical to delineate the chemical signatures of amyloid aggregation in these two vascular dementias. This in turn will increase the knowledge on the pathophysiology of these diseases and the pathogenic role of heterogenous amyloid peptide interactions and deposition, respectively. Herein, we used matrix-assisted laser desorption/ionization mass spectrometry imaging (MALDI-MSI) in combination with hyperspectral, confocal microscopy based on luminescent conjugated oligothiophene probes (LCO) to delineate the structural traits and associated amyloid peptide patterns of single CAA in postmortem brain tissue of patients with FBD, FDD as well as sporadic CAA without AD (CAA+) that show pronounced CAA without parenchymal plaques. The results show that CAA in both FBD and FDD consist of N-terminally truncated- and pyroglutamate-modified amyloid peptide species (ADan and ABri), but that ADan peptides in FDD are also extensively C-terminally truncated as compared to ABri in FBD, which contributes to hydrophobicity of ADan species. Further, CAA in FDD showed co-deposition with A\u03b2 x-42 and A\u03b2 x-40 species. CAA+ vessels were structurally more mature than FDD/FBD CAA and contained significant amounts of pyroglutamated A\u03b2. When compared with FDD, A\u03b2 in CAA+ showed more C-terminal and less N-terminally truncations. In FDD, ADan showed spatial co-localization with A\u03b23pE-40 and A\u03b23-40 but not with A\u03b2x-42 species. This suggests an increased aggregation propensity of A\u03b2 in FDD that promotes co-aggregation of both A\u03b2 and ADan. Further, CAA maturity appears to be mainly governed by A\u03b2 content based on the significantly higher 500/580 patterns observed in CAA+ than in FDD and FBD, respectively. Together this is the first study of its kind on comprehensive delineation of Bri2 and APP-derived amyloid peptides in single vascular plaques in both FDD/FBD and sporadic CAA that provides new insight in non-AD-related vascular amyloid pathology. Cover Image for this issue: https://doi.org/10.1111/jnc.15424.", "doi": "10.1111/jnc.15694", "pmid": "36102248", "labels": {"Integrated Microscopy Technologies Gothenburg": "Collaborative"}, "xrefs": [{"db": "pmc", "key": "PMC9828067"}], "notes": [], "created": "2023-02-16T08:26:18.918Z", "modified": "2023-06-19T13:39:16.927Z"}, {"entity": "publication", "iuid": "9df626ba4dd2425eb13ec942e2a40efc", "links": {"self": {"href": "https://publications.scilifelab.se/publication/9df626ba4dd2425eb13ec942e2a40efc.json"}, "display": {"href": "https://publications.scilifelab.se/publication/9df626ba4dd2425eb13ec942e2a40efc"}}, "title": "Cerebrospinal fluid proteomic study of two bipolar disorder cohorts.", "authors": [{"family": "Isgren", "given": "Anniella", "initials": "A", "orcid": "0000-0003-1901-6988", "researcher": {"href": "https://publications.scilifelab.se/researcher/07b132c4700745a695ddb6a3ce946e9d.json"}}, {"family": "G\u00f6teson", "given": "Andreas", "initials": "A", "orcid": "0000-0001-6118-6054", "researcher": {"href": "https://publications.scilifelab.se/researcher/ddb9372de0984261bce8b2ebdeee26ee.json"}}, {"family": "Holm\u00e9n-Larsson", "given": "Jessica", "initials": "J"}, {"family": "Pelanis", "given": "Aurimantas", "initials": "A"}, {"family": "Sellgren", "given": "Carl", "initials": "C"}, {"family": "Joas", "given": "Erik", "initials": "E"}, {"family": "Sparding", "given": "Timea", "initials": "T"}, {"family": "Zetterberg", "given": "Henrik", "initials": "H", "orcid": "0000-0003-3930-4354", "researcher": {"href": "https://publications.scilifelab.se/researcher/85efee74eb4a4b38b63cf2823d204529.json"}}, {"family": "Smedler", "given": "Erik", "initials": "E"}, {"family": "Jakobsson", "given": "Joel", "initials": "J"}, {"family": "Land\u00e9n", "given": "Mikael", "initials": "M", "orcid": "0000-0002-4496-6451", "researcher": {"href": "https://publications.scilifelab.se/researcher/792e2b8b8da94572a4d2815703d29749.json"}}], "type": "journal article", "published": "2022-08-19", "journal": {"title": "Mol. Psychiatry", "issn": "1476-5578", "issn-l": "1359-4184"}, "abstract": "The pathophysiology of bipolar disorder remains to be elucidated and there are no diagnostic or prognostic biomarkers for the condition. In this explorative proteomic study, we analyzed 201 proteins in cerebrospinal fluid (CSF) from mood stable bipolar disorder patients and control subjects sampled from two independent cohorts, amounting to a total of 204 patients and 144 controls. We used three Olink Multiplex panels, whereof one specifically targets immune biomarkers, to assess a broad set of CSF protein concentrations. After quality control and removal of proteins with a low detection rate, 105 proteins remained for analyses in relation to case-control status and clinical variables. Only case-control differences that replicated across cohorts were considered. Results adjusted for potential confounders showed that CSF concentrations of growth hormone were lower in bipolar disorder compared with controls in both cohorts. The effect size was larger when the analysis was restricted to bipolar disorder type 1 and controls. We found no indications of immune activation or other aberrations. Growth hormone exerts many effects in the central nervous system and our findings suggest that growth hormone might be implicated in the pathophysiology of bipolar disorder.", "doi": "10.1038/s41380-022-01724-2", "pmid": "35986174", "labels": {"Affinity Proteomics Uppsala": "Service"}, "xrefs": [{"db": "pii", "key": "10.1038/s41380-022-01724-2"}], "notes": [], "created": "2022-12-02T08:47:01.362Z", "modified": "2022-12-02T08:47:01.486Z"}, {"entity": "publication", "iuid": "4d938430321a45eea09d9bb81bc35a1c", "links": {"self": {"href": "https://publications.scilifelab.se/publication/4d938430321a45eea09d9bb81bc35a1c.json"}, "display": {"href": "https://publications.scilifelab.se/publication/4d938430321a45eea09d9bb81bc35a1c"}}, "title": "Structural amyloid plaque polymorphism is associated with distinct lipid accumulations revealed by trapped ion mobility mass spectrometry imaging.", "authors": [{"family": "Michno", "given": "Wojciech", "initials": "W", "orcid": "0000-0002-3096-3604", "researcher": {"href": "https://publications.scilifelab.se/researcher/7b4307eb6e45426e8176337e88c9c344.json"}}, {"family": "Wehrli", "given": "Patrick M", "initials": "PM"}, {"family": "Koutarapu", "given": "Srinivas", "initials": "S"}, {"family": "Marsching", "given": "Christian", "initials": "C"}, {"family": "Minta", "given": "Karolina", "initials": "K"}, {"family": "Ge", "given": "Junyue", "initials": "J"}, {"family": "Meyer", "given": "Sven W", "initials": "SW"}, {"family": "Zetterberg", "given": "Henrik", "initials": "H", "orcid": "0000-0003-3930-4354", "researcher": {"href": "https://publications.scilifelab.se/researcher/85efee74eb4a4b38b63cf2823d204529.json"}}, {"family": "Blennow", "given": "Kaj", "initials": "K"}, {"family": "Henkel", "given": "Corinna", "initials": "C"}, {"family": "Oetjen", "given": "Janina", "initials": "J", "orcid": "0000-0002-4088-5742", "researcher": {"href": "https://publications.scilifelab.se/researcher/aa10e19731a847d1a6810778bcdee4fe.json"}}, {"family": "Hopf", "given": "Carsten", "initials": "C", "orcid": "0000-0003-0802-6451", "researcher": {"href": "https://publications.scilifelab.se/researcher/178878399aac4cd6bf793f3720c75365.json"}}, {"family": "Hanrieder", "given": "J\u00f6rg", "initials": "J", "orcid": "0000-0001-6059-198X", "researcher": {"href": "https://publications.scilifelab.se/researcher/4e65454100674f98bf8f2575093f2441.json"}}], "type": "journal article", "published": "2022-02-00", "journal": {"title": "J. Neurochem.", "issn": "1471-4159", "volume": "160", "issue": "4", "pages": "482-498", "issn-l": "0022-3042"}, "abstract": "Understanding of Alzheimer's disease (AD) pathophysiology requires molecular assessment of how key pathological factors, specifically amyloid \u03b2 (A\u03b2) plaques, influence the surrounding microenvironment. Here, neuronal lipids have been implicated in A\u03b2 plaque pathology, though the lipid microenvironment in direct proximity to A\u03b2 plaques is still not fully resolved. A further challenge is the microenvironmental molecular heterogeneity, across structurally polymorphic A\u03b2 features, such as diffuse, immature, and mature, fibrillary aggregates, whose resolution requires the integration of advanced, multimodal chemical imaging tools. Herein, we used matrix-assisted laser desorption/ionization trapped ion mobility spectrometry time-of-flight based mass spectrometry imaging (MALDI TIMS TOF MSI) in combination with hyperspectral confocal microscopy to probe the lipidomic microenvironment associated with structural polymorphism of A\u03b2 plaques in transgenic Alzheimer's disease mice (tgAPPSWE ). Using on tissue and ex situ validation, TIMS MS/MS facilitated unambiguous identification of isobaric lipid species that showed plaque pathology-associated localizations. Integrated multivariate imaging data analysis revealed multiple, A\u03b2 plaque-enriched lipid patterns for gangliosides (GM), phosphoinositols (PI), phosphoethanolamines (PE), and phosphatidic acids (PA). Conversely, sulfatides (ST), cardiolipins (CL), and polyunsaturated fatty acid (PUFA)-conjugated phosphoserines (PS), and PE were depleted at plaques. Hyperspectral amyloid imaging further delineated the unique distribution of PA and PE species to mature plaque core regions, while PI, LPI, GM2 and GM3 lipids localized to immature A\u03b2 aggregates present within the periphery of A\u03b2 plaques. Finally, we followed AD pathology-associated lipid changes over time, identifying plaque- growth and maturation to be characterized by peripheral accumulation of PI (18:0/22:6). Together, these data demonstrate the potential of multimodal imaging approaches to overcome limitations associated with conventional advanced MS imaging applications. This allowed for the differentiation of both distinct lipid components in a complex micro-environment as well as their correlation to disease-relevant amyloid plaque polymorphs. Cover Image for this issue: https://doi.org/10.1111/jnc.15390.", "doi": "10.1111/jnc.15557", "pmid": "34882796", "labels": {"Integrated Microscopy Technologies Gothenburg": "Collaborative"}, "xrefs": [], "notes": [], "created": "2023-02-16T08:24:46.768Z", "modified": "2023-02-16T08:24:46.828Z"}, {"entity": "publication", "iuid": "ce17f3a9d09243a5991a765d05d88a73", "links": {"self": {"href": "https://publications.scilifelab.se/publication/ce17f3a9d09243a5991a765d05d88a73.json"}, "display": {"href": "https://publications.scilifelab.se/publication/ce17f3a9d09243a5991a765d05d88a73"}}, "title": "Cerebrospinal fluid proteomics targeted for central nervous system processes in bipolar disorder.", "authors": [{"family": "G\u00f6teson", "given": "Andreas", "initials": "A", "orcid": "0000-0001-6118-6054", "researcher": {"href": "https://publications.scilifelab.se/researcher/ddb9372de0984261bce8b2ebdeee26ee.json"}}, {"family": "Isgren", "given": "Anniella", "initials": "A"}, {"family": "Jonsson", "given": "Lina", "initials": "L"}, {"family": "Sparding", "given": "Timea", "initials": "T"}, {"family": "Smedler", "given": "Erik", "initials": "E"}, {"family": "Pelanis", "given": "Aurimantas", "initials": "A"}, {"family": "Zetterberg", "given": "Henrik", "initials": "H", "orcid": "0000-0003-3930-4354", "researcher": {"href": "https://publications.scilifelab.se/researcher/85efee74eb4a4b38b63cf2823d204529.json"}}, {"family": "Jakobsson", "given": "Joel", "initials": "J"}, {"family": "P\u00e5lsson", "given": "Erik", "initials": "E"}, {"family": "Holm\u00e9n-Larsson", "given": "Jessica", "initials": "J"}, {"family": "Land\u00e9n", "given": "Mikael", "initials": "M", "orcid": "0000-0002-4496-6451", "researcher": {"href": "https://publications.scilifelab.se/researcher/792e2b8b8da94572a4d2815703d29749.json"}}], "type": "journal article", "published": "2021-12-00", "journal": {"title": "Mol. Psychiatry", "issn": "1476-5578", "volume": "26", "issue": "12", "pages": "7446-7453", "issn-l": "1359-4184"}, "abstract": "The etiopathology of bipolar disorder is largely unknown. We collected cerebrospinal fluid (CSF) samples from two independent case-control cohorts (total n = 351) to identify proteins associated with bipolar disorder. A panel of 92 proteins targeted towards central nervous system processes identified two proteins that replicated across the cohorts: the CSF concentrations of testican-1 were lower, and the CSF concentrations of C-type lectin domain family 1 member B (CLEC1B) were higher, in cases than controls. In a restricted subgroup analysis, we compared only bipolar type 1 with controls and identified two additional proteins that replicated in both cohorts: draxin and tumor necrosis factor receptor superfamily member 21 (TNFRSF21), both lower in cases than controls. This analysis additionally revealed several proteins significantly associated with bipolar type 1 in one cohort, falling just short of replicated statistical significance in the other (tenascin-R, disintegrin and metalloproteinase domain-containing protein 23, cell adhesion molecule 3, RGM domain family member B, plexin-B1, and brorin). Next, we conducted genome-wide association analyses of the case-control-associated proteins. In these analyses, we found associations with the voltage-gated calcium channel subunit CACNG4, and the lipid-droplet-associated gene PLIN5 with CSF concentrations of TNFRSF21 and CLEC1B, respectively. The reported proteins are involved in neuronal cell-cell and cell-matrix interactions, particularly in the developing brain, and in pathways of importance for lithium's mechanism of action. In summary, we report four novel CSF protein associations with bipolar disorder that replicated in two independent case-control cohorts, shedding new light on the central nervous system processes implicated in bipolar disorder.", "doi": "10.1038/s41380-021-01236-5", "pmid": "34349225", "labels": {"Affinity Proteomics Uppsala": "Service"}, "xrefs": [{"db": "pii", "key": "10.1038/s41380-021-01236-5"}], "notes": [], "created": "2021-12-10T09:06:20.729Z", "modified": "2022-12-02T08:56:13.821Z"}, {"entity": "publication", "iuid": "5bd96c5ba07a441284381c33d5ac429b", "links": {"self": {"href": "https://publications.scilifelab.se/publication/5bd96c5ba07a441284381c33d5ac429b.json"}, "display": {"href": "https://publications.scilifelab.se/publication/5bd96c5ba07a441284381c33d5ac429b"}}, "title": "The localization of amyloid precursor protein to ependymal cilia in vertebrates and its role in ciliogenesis and brain development in zebrafish.", "authors": [{"family": "Chebli", "given": "Jasmine", "initials": "J", "orcid": "0000-0003-0791-3198", "researcher": {"href": "https://publications.scilifelab.se/researcher/0b0dd51631ce4c3c89a98b9d6c7d3d35.json"}}, {"family": "Rahmati", "given": "Maryam", "initials": "M"}, {"family": "Lashley", "given": "Tammaryn", "initials": "T", "orcid": "0000-0001-7389-0348", "researcher": {"href": "https://publications.scilifelab.se/researcher/533fe74a716840b2a55fddf0452f2a23.json"}}, {"family": "Edeman", "given": "Brigitta", "initials": "B"}, {"family": "Oldfors", "given": "Anders", "initials": "A", "orcid": "0000-0002-5758-7397", "researcher": {"href": "https://publications.scilifelab.se/researcher/e82034663f6647cd9827871bfca633ef.json"}}, {"family": "Zetterberg", "given": "Henrik", "initials": "H", "orcid": "0000-0003-3930-4354", "researcher": {"href": "https://publications.scilifelab.se/researcher/85efee74eb4a4b38b63cf2823d204529.json"}}, {"family": "Abramsson", "given": "Alexandra", "initials": "A", "orcid": "0000-0002-4715-9225", "researcher": {"href": "https://publications.scilifelab.se/researcher/7abde12dab2e4d338bc6e55933f07531.json"}}], "type": "journal article", "published": "2021-09-27", "journal": {"title": "Sci Rep", "issn": "2045-2322", "volume": "11", "issue": "1", "pages": "19115", "issn-l": "2045-2322"}, "abstract": "Amyloid precursor protein (APP) is expressed in many tissues in human, mice and in zebrafish. In zebrafish, there are two orthologues, Appa and Appb. Interestingly, some cellular processes associated with APP overlap with cilia-mediated functions. Whereas the localization of APP to primary cilia of in vitro-cultured cells has been reported, we addressed the presence of APP in motile and in non-motile sensory cilia and its potential implication for ciliogenesis using zebrafish, mouse, and human samples. We report that Appa and Appb are expressed by ciliated cells and become localized at the membrane of cilia in the olfactory epithelium, otic vesicle and in the brain ventricles of zebrafish embryos. App in ependymal cilia persisted in adult zebrafish and was also detected in mouse and human brain. Finally, we found morphologically abnormal ependymal cilia and smaller brain ventricles in appa-/-appb-/- mutant zebrafish. Our findings demonstrate an evolutionary conserved localisation of APP to cilia and suggest a role of App in ciliogenesis and cilia-related functions.", "doi": "10.1038/s41598-021-98487-7", "pmid": "34580355", "labels": {"Integrated Microscopy Technologies Gothenburg": "Service"}, "xrefs": [{"db": "pmc", "key": "PMC8476544"}, {"db": "pii", "key": "10.1038/s41598-021-98487-7"}], "notes": [], "created": "2023-02-16T08:14:17.553Z", "modified": "2023-02-16T08:14:17.703Z"}, {"entity": "publication", "iuid": "cef437ec472748d99c04192947b80bd4", "links": {"self": {"href": "https://publications.scilifelab.se/publication/cef437ec472748d99c04192947b80bd4.json"}, "display": {"href": "https://publications.scilifelab.se/publication/cef437ec472748d99c04192947b80bd4"}}, "title": "Genome-scale metabolic network reconstruction of model animals as a platform for translational research.", "authors": [{"family": "Wang", "given": "Hao", "initials": "H", "orcid": "0000-0001-7475-0136", "researcher": {"href": "https://publications.scilifelab.se/researcher/836b4fbf7ebd4f80abc84465c8f29a2e.json"}}, {"family": "Robinson", "given": "Jonathan L", "initials": "JL", "orcid": "0000-0001-8567-5960", "researcher": {"href": "https://publications.scilifelab.se/researcher/b70b6d9b64fd45e882c4108aded013d4.json"}}, {"family": "Kocabas", "given": "Pinar", "initials": "P", "orcid": "0000-0001-9788-2019", "researcher": {"href": "https://publications.scilifelab.se/researcher/c89eb03e619945a2a2058179b0d0e310.json"}}, {"family": "Gustafsson", "given": "Johan", "initials": "J", "orcid": "0000-0001-5072-2659", "researcher": {"href": "https://publications.scilifelab.se/researcher/bd5fda1ac79e49c185ba6f4dfcdff5fc.json"}}, {"family": "Anton", "given": "Mihail", "initials": "M", "orcid": "0000-0002-7753-9042", "researcher": {"href": "https://publications.scilifelab.se/researcher/4a28ecc2261e436ea5884ada5e512aed.json"}}, {"family": "Cholley", "given": "Pierre-Etienne", "initials": "PE"}, {"family": "Huang", "given": "Shan", "initials": "S"}, {"family": "Gobom", "given": "Johan", "initials": "J"}, {"family": "Svensson", "given": "Thomas", "initials": "T", "orcid": "0000-0002-9190-2979", "researcher": {"href": "https://publications.scilifelab.se/researcher/dc636683ece84dc4ac3e4d10df0c7a49.json"}}, {"family": "Uhlen", "given": "Mattias", "initials": "M", "orcid": "0000-0002-4858-8056", "researcher": {"href": "https://publications.scilifelab.se/researcher/ff81da3cb0cf4262873b993a1b06798c.json"}}, {"family": "Zetterberg", "given": "Henrik", "initials": "H", "orcid": "0000-0003-3930-4354", "researcher": {"href": "https://publications.scilifelab.se/researcher/85efee74eb4a4b38b63cf2823d204529.json"}}, {"family": "Nielsen", "given": "Jens", "initials": "J", "orcid": "0000-0002-9955-6003", "researcher": {"href": "https://publications.scilifelab.se/researcher/7a596e289be4438a8a2653b1f25fea8b.json"}}], "type": "journal article", "published": "2021-07-27", "journal": {"title": "Proc. Natl. Acad. Sci. U.S.A.", "issn": "1091-6490", "volume": "118", "issue": "30", "pages": "e2102344118", "issn-l": "0027-8424"}, "abstract": "Genome-scale metabolic models (GEMs) are used extensively for analysis of mechanisms underlying human diseases and metabolic malfunctions. However, the lack of comprehensive and high-quality GEMs for model organisms restricts translational utilization of omics data accumulating from the use of various disease models. Here we present a unified platform of GEMs that covers five major model animals, including Mouse1 (Mus musculus), Rat1 (Rattus norvegicus), Zebrafish1 (Danio rerio), Fruitfly1 (Drosophila melanogaster), and Worm1 (Caenorhabditis elegans). These GEMs represent the most comprehensive coverage of the metabolic network by considering both orthology-based pathways and species-specific reactions. All GEMs can be interactively queried via the accompanying web portal Metabolic Atlas. Specifically, through integrative analysis of Mouse1 with RNA-sequencing data from brain tissues of transgenic mice we identified a coordinated up-regulation of lysosomal GM2 ganglioside and peptide degradation pathways which appears to be a signature metabolic alteration in Alzheimer's disease (AD) mouse models with a phenotype of amyloid precursor protein overexpression. This metabolic shift was further validated with proteomics data from transgenic mice and cerebrospinal fluid samples from human patients. The elevated lysosomal enzymes thus hold potential to be used as a biomarker for early diagnosis of AD. Taken together, we foresee that this evolving open-source platform will serve as an important resource to facilitate the development of systems medicines and translational biomedical applications.", "doi": "10.1073/pnas.2102344118", "pmid": "34282017", "labels": {"Bioinformatics Support, Infrastructure and Training": "Collaborative", "Systems Biology": "Technology development", "Bioinformatics Support for Computational Resources": "Service", "Bioinformatics (NBIS)": "Collaborative"}, "xrefs": [{"db": "pii", "key": "2102344118"}, {"db": "pmc", "key": "PMC8325244"}], "notes": [], "created": "2021-08-19T08:56:58.316Z", "modified": "2024-01-16T13:48:39.079Z"}, {"entity": "publication", "iuid": "e430feac4bdd43b18fefd962d8122973", "links": {"self": {"href": "https://publications.scilifelab.se/publication/e430feac4bdd43b18fefd962d8122973.json"}, "display": {"href": "https://publications.scilifelab.se/publication/e430feac4bdd43b18fefd962d8122973"}}, "title": "Severe COVID-19 in an APS1 patient with interferon autoantibodies treated with plasmapheresis", "authors": [{"family": "Lemarquis", "given": "Andri", "initials": "A", "orcid": "0000-0001-5165-0247", "researcher": {"href": "https://publications.scilifelab.se/researcher/776e9a2ecebf446ba4d0e3d20c8d793c.json"}}, {"family": "Campbell", "given": "Tessa", "initials": "T", "orcid": "0000-0002-7737-2123", "researcher": {"href": "https://publications.scilifelab.se/researcher/649b3cbdbb894026ba87a79e6834e651.json"}}, {"family": "Aranda-Guill\u00e9n", "given": "Maribel", "initials": "M", "orcid": "0000-0003-0050-704X", "researcher": {"href": "https://publications.scilifelab.se/researcher/65dc88b917274bc595daed855b63abab.json"}}, {"family": "Hennings", "given": "Viktoria", "initials": "V"}, {"family": "Brodin", "given": "Petter", "initials": "P", "orcid": "0000-0002-8103-0046", "researcher": {"href": "https://publications.scilifelab.se/researcher/40097353cdb24e52bf2330eb687042bf.json"}}, {"family": "K\u00e4mpe", "given": "Olle", "initials": "O", "orcid": "0000-0001-6091-9914", "researcher": {"href": "https://publications.scilifelab.se/researcher/2c547dc809a14cdaa47b623cf638162b.json"}}, {"family": "Blennow", "given": "Kaj", "initials": "K", "orcid": "0000-0002-1890-4193", "researcher": {"href": "https://publications.scilifelab.se/researcher/5e646be026ce42ecbfd4d62eca3f9bce.json"}}, {"family": "Zetterberg", "given": "Henrik", "initials": "H", "orcid": "0000-0003-3930-4354", "researcher": {"href": "https://publications.scilifelab.se/researcher/85efee74eb4a4b38b63cf2823d204529.json"}}, {"family": "Wenner\u00e5s", "given": "Christine", "initials": "C"}, {"family": "Eriksson", "given": "Kristina", "initials": "K"}, {"family": "Landegren", "given": "Nils", "initials": "N", "orcid": "0000-0002-6163-9540", "researcher": {"href": "https://publications.scilifelab.se/researcher/13ceacb17b7448709f9bfcd593bec1e2.json"}}, {"family": "Bryceson", "given": "Yenan", "initials": "Y", "orcid": "0000-0002-7783-9934", "researcher": {"href": "https://publications.scilifelab.se/researcher/ce63349a03924444836215ffd201d2e3.json"}}, {"family": "Berg", "given": "Stefan", "initials": "S"}, {"family": "Ekwall", "given": "Olov", "initials": "O", "orcid": "0000-0002-4506-9955", "researcher": {"href": "https://publications.scilifelab.se/researcher/2d7af11d7d30410d8fe5f3b5fbd0ba1d.json"}}], "type": "journal-article", "published": "2021-07-00", "journal": {"title": "Journal of Allergy and Clinical Immunology", "issn": "1085-8725", "volume": "148", "issue": "1", "pages": "96-98", "issn-l": "0091-6749"}, "abstract": null, "doi": "10.1016/j.jaci.2021.03.034", "pmid": "33892926", "labels": {"Autoimmunity and Serology Profiling": "Service"}, "xrefs": [{"db": "pmc", "key": "PMC8051851"}, {"db": "pii", "key": "S0091-6749(21)00556-X"}], "notes": [], "created": "2022-11-10T22:49:31.895Z", "modified": "2023-06-19T11:52:47.010Z"}, {"entity": "publication", "iuid": "b70be864396f40b68d30939cc4e01962", "links": {"self": {"href": 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"researcher": {"href": "https://publications.scilifelab.se/researcher/e390c82cf4cb4075a20c2f2858912ec6.json"}}, {"family": "Garc\u00eda-Alberca", "given": "Jose Mar\u00eda", "initials": "JM", "orcid": "0000-0003-2951-6644", "researcher": {"href": "https://publications.scilifelab.se/researcher/ee94f765be9142b1a405878dfc8d5fb0.json"}}, {"family": "Bullido", "given": "Mar\u00eda J", "initials": "MJ", "orcid": "0000-0002-6477-1117", "researcher": {"href": "https://publications.scilifelab.se/researcher/5b16229b634f4ed38b8825c3bdf30a4b.json"}}, {"family": "\u00c1lvarez", "given": "Victoria", "initials": "V"}, {"family": "Lle\u00f3", "given": "Alberto", "initials": "A", "orcid": "0000-0002-2568-5478", "researcher": {"href": "https://publications.scilifelab.se/researcher/0f93b0e1f2b0458ea41339b0935e892b.json"}}, {"family": "Real", "given": "Luis M", "initials": "LM", "orcid": "0000-0003-4932-7429", "researcher": {"href": "https://publications.scilifelab.se/researcher/7566022edb8d47309631222dcf07bd01.json"}}, {"family": "Mir", "given": "Pablo", "initials": "P"}, {"family": "Medina", "given": "Miguel", "initials": "M", "orcid": "0000-0002-7016-5340", "researcher": {"href": "https://publications.scilifelab.se/researcher/f8bdf4999e6c495fa1e101fdf479701a.json"}}, {"family": "Scheltens", "given": "Philip", "initials": "P"}, {"family": "Holstege", "given": "Henne", "initials": "H", "orcid": "0000-0002-7688-3087", "researcher": {"href": "https://publications.scilifelab.se/researcher/bbb3fd35354e428eb2596e9806db5b9e.json"}}, {"family": "Marqui\u00e9", "given": "Marta", "initials": "M"}, {"family": "S\u00e1ez", "given": "Mar\u00eda Eugenia", "initials": "ME", "orcid": "0000-0001-9299-2534", "researcher": {"href": "https://publications.scilifelab.se/researcher/d2d2767678914111968cfecaff39ed01.json"}}, {"family": "Carracedo", "given": "\u00c1ngel", "initials": "\u00c1"}, {"family": "Amouyel", "given": "Philippe", "initials": "P", "orcid": "0000-0001-9088-234X", "researcher": {"href": "https://publications.scilifelab.se/researcher/0d82379a59334fcb8cdbc74a04c56765.json"}}, {"family": "Schellenberg", "given": "Gerard D", "initials": "GD"}, {"family": "Williams", "given": "Julie", "initials": "J", "orcid": "0000-0002-4069-0259", "researcher": {"href": "https://publications.scilifelab.se/researcher/0f566fcdd8bd453eb1f3a6953e29451c.json"}}, {"family": "Seshadri", "given": "Sudha", "initials": "S", "orcid": "0000-0001-6135-2622", "researcher": {"href": "https://publications.scilifelab.se/researcher/429e370668ec47ce9945bc5262dccbb3.json"}}, {"family": "van Duijn", "given": "Cornelia M", "initials": "CM", "orcid": "0000-0002-2374-9204", "researcher": {"href": "https://publications.scilifelab.se/researcher/354ccf94e95f40da96e61c89a0a60adb.json"}}, {"family": "Mather", "given": "Karen A", "initials": "KA", "orcid": "0000-0003-4143-8941", "researcher": {"href": "https://publications.scilifelab.se/researcher/ec0c7f15235d4be4848b56025d5ff4f0.json"}}, {"family": "S\u00e1nchez-Valle", "given": "Raquel", "initials": "R"}, {"family": "Serrano-R\u00edos", "given": "Manuel", "initials": "M"}, {"family": "Orellana", "given": "Adelina", "initials": "A"}, {"family": "T\u00e1rraga", "given": "Llu\u00eds", "initials": "L"}, {"family": "Blennow", "given": "Kaj", "initials": "K", "orcid": "0000-0002-1890-4193", "researcher": {"href": "https://publications.scilifelab.se/researcher/5e646be026ce42ecbfd4d62eca3f9bce.json"}}, {"family": "Huisman", "given": "Martijn", "initials": "M"}, {"family": "Andreassen", "given": "Ole A", "initials": "OA", "orcid": "0000-0002-4461-3568", "researcher": {"href": "https://publications.scilifelab.se/researcher/56f384e8e2fd4a7383c7b26e88a828b2.json"}}, {"family": "Posthuma", "given": "Danielle", "initials": "D"}, {"family": "Clarim\u00f3n", "given": "Jordi", "initials": "J"}, {"family": "Boada", "given": "Merc\u00e8", "initials": "M", "orcid": "0000-0003-2617-3009", "researcher": {"href": "https://publications.scilifelab.se/researcher/c8d00c33569e41b481cf5cdc99cd96e9.json"}}, {"family": "van der Flier", "given": "Wiesje M", "initials": "WM", "orcid": "0000-0001-8766-6224", "researcher": {"href": "https://publications.scilifelab.se/researcher/0b32776a9e524f299765506b6dbe9768.json"}}, {"family": "Ramirez", "given": "Alfredo", "initials": "A", "orcid": "0000-0003-4991-763X", "researcher": {"href": "https://publications.scilifelab.se/researcher/a8995a57e82f4f479ab8251175aeb8d6.json"}}, {"family": "Lambert", "given": "Jean-Charles", "initials": "JC", "orcid": "0000-0003-0829-7817", "researcher": {"href": "https://publications.scilifelab.se/researcher/a0ec452344144906b7e8be95eb8c62d6.json"}}, {"family": "van der Lee", "given": "Sven J", "initials": "SJ", "orcid": "0000-0003-1606-8643", "researcher": {"href": "https://publications.scilifelab.se/researcher/9a34a1b7b98b4360b48dafe3f0d5dcb2.json"}}, {"family": "Ruiz", "given": "Agust\u00edn", "initials": "A", "orcid": "0000-0003-2633-2495", "researcher": {"href": "https://publications.scilifelab.se/researcher/33a263bd6bd24ca897c988d4fcbcaca1.json"}}], "type": "journal article", "published": "2021-06-07", "journal": {"title": "Nat Commun", "issn": "2041-1723", "issn-l": "2041-1723", "volume": "12", "issue": "1", "pages": "3417"}, "abstract": "Genetic discoveries of Alzheimer's disease are the drivers of our understanding, and together with polygenetic risk stratification can contribute towards planning of feasible and efficient preventive and curative clinical trials. We first perform a large genetic association study by merging all available case-control datasets and by-proxy study results (discovery n = 409,435 and validation size n = 58,190). Here, we add six variants associated with Alzheimer's disease risk (near APP, CHRNE, PRKD3/NDUFAF7, PLCG2 and two exonic variants in the SHARPIN gene). Assessment of the polygenic risk score and stratifying by APOE reveal a 4 to 5.5 years difference in median age at onset of Alzheimer's disease patients in APOE \u025b4 carriers. Because of this study, the underlying mechanisms of APP can be studied to refine the amyloid cascade and the polygenic risk score provides a tool to select individuals at high risk of Alzheimer's disease.", "doi": "10.1038/s41467-021-22491-8", "pmid": "34099642", "labels": {"NGI Uppsala (SNP&SEQ Technology Platform)": "Service", "National Genomics Infrastructure": "Service"}, "xrefs": [{"db": "pmc", "key": "PMC8184987"}, {"db": "pii", "key": "10.1038/s41467-021-22491-8"}], "notes": [], "created": "2021-08-19T13:41:32.762Z", "modified": "2023-06-20T15:56:47.699Z"}, {"entity": "publication", "iuid": "ac498053fd134ab2a54ce6b4b2ed366c", "links": {"self": {"href": "https://publications.scilifelab.se/publication/ac498053fd134ab2a54ce6b4b2ed366c.json"}, "display": {"href": "https://publications.scilifelab.se/publication/ac498053fd134ab2a54ce6b4b2ed366c"}}, "title": "Following spatial A\u03b2 aggregation dynamics in evolving Alzheimer's disease pathology by imaging stable isotope labeling kinetics.", "authors": [{"family": "Michno", "given": "Wojciech", "initials": "W", "orcid": "0000-0002-3096-3604", "researcher": {"href": "https://publications.scilifelab.se/researcher/7b4307eb6e45426e8176337e88c9c344.json"}}, {"family": "Stringer", "given": "Katie M", "initials": "KM", "orcid": "0000-0003-1616-2437", "researcher": {"href": "https://publications.scilifelab.se/researcher/c2638dd298ce470eb41bb45cbf1501c3.json"}}, {"family": "Enzlein", "given": "Thomas", "initials": "T", "orcid": "0000-0003-1789-4090", "researcher": {"href": "https://publications.scilifelab.se/researcher/8c32c7c836c4417182d0b04ac914e318.json"}}, {"family": "Passarelli", "given": "Melissa K", "initials": "MK", "orcid": "0000-0003-2466-1439", "researcher": {"href": "https://publications.scilifelab.se/researcher/2699b550e880407296571ccfe51a1cee.json"}}, {"family": "Escrig", "given": "Stephane", "initials": "S", "orcid": "0000-0002-7525-4000", "researcher": {"href": "https://publications.scilifelab.se/researcher/5f704fbd587f4a96b272ea9269512c89.json"}}, {"family": "Vitanova", "given": "Karina", "initials": "K", "orcid": "0000-0001-8800-4150", "researcher": {"href": "https://publications.scilifelab.se/researcher/c3c495f6ef37496fbafc13a93a8d50f3.json"}}, {"family": "Wood", "given": "Jack", "initials": "J", "orcid": "0000-0001-6049-4020", "researcher": {"href": "https://publications.scilifelab.se/researcher/a9b71cccc5da4ece9a9f57f0c46eda26.json"}}, {"family": "Blennow", "given": "Kaj", "initials": "K", "orcid": "0000-0002-1890-4193", "researcher": {"href": "https://publications.scilifelab.se/researcher/5e646be026ce42ecbfd4d62eca3f9bce.json"}}, {"family": "Zetterberg", "given": "Henrik", "initials": "H", "orcid": "0000-0003-3930-4354", "researcher": {"href": "https://publications.scilifelab.se/researcher/85efee74eb4a4b38b63cf2823d204529.json"}}, {"family": "Meibom", "given": "Anders", "initials": "A", "orcid": "0000-0002-4542-2819", "researcher": {"href": "https://publications.scilifelab.se/researcher/449ed37aa5ab48ab8b1d93e0ab0f3f9b.json"}}, {"family": "Hopf", "given": "Carsten", "initials": "C", "orcid": "0000-0003-0802-6451", "researcher": {"href": "https://publications.scilifelab.se/researcher/178878399aac4cd6bf793f3720c75365.json"}}, {"family": "Edwards", "given": "Frances A", "initials": "FA", "orcid": "0000-0001-8515-9077", "researcher": {"href": "https://publications.scilifelab.se/researcher/bdb5831ebd95409b9fc30c2410bf8ad3.json"}}, {"family": "Hanrieder", "given": "J\u00f6rg", "initials": "J", "orcid": "0000-0001-6059-198X", "researcher": {"href": "https://publications.scilifelab.se/researcher/4e65454100674f98bf8f2575093f2441.json"}}], "type": "journal article", "published": "2021-06-00", "journal": {"title": "Sci Adv", "issn": "2375-2548", "volume": "7", "issue": "25", "issn-l": "2375-2548"}, "abstract": "\u03b2-Amyloid (A\u03b2) plaque formation is the major pathological hallmark of Alzheimer's disease (AD) and constitutes a potentially critical, early inducer driving AD pathogenesis as it precedes other pathological events and cognitive symptoms by decades. It is therefore critical to understand how A\u03b2 pathology is initiated and where and when distinct A\u03b2 species aggregate. Here, we used metabolic isotope labeling in APP knock-in mice together with mass spectrometry imaging to monitor the earliest seeds of A\u03b2 deposition through ongoing plaque development. This allowed visualizing A\u03b2 aggregation dynamics within single plaques across different brain regions. We show that formation of structurally distinct plaques is associated with differential A\u03b2 peptide deposition. Specifically, A\u03b21-42 is forming an initial core structure followed by radial outgrowth and late secretion and deposition of A\u03b21-38. These data describe a detailed picture of the earliest events of precipitating amyloid pathology at scales not previously possible.NL-G-F", "doi": "10.1126/sciadv.abg4855", "pmid": "34134980", "labels": {"Integrated Microscopy Technologies Gothenburg": "Collaborative"}, "xrefs": [{"db": "pmc", "key": "PMC8208724"}, {"db": "pii", "key": "7/25/eabg4855"}], "notes": [], "created": "2023-02-16T08:19:47.219Z", "modified": "2023-02-16T08:19:47.531Z"}, {"entity": "publication", "iuid": "b3c72707ac064b0c8c7434c3d0f93d4c", "links": {"self": {"href": "https://publications.scilifelab.se/publication/b3c72707ac064b0c8c7434c3d0f93d4c.json"}, "display": {"href": "https://publications.scilifelab.se/publication/b3c72707ac064b0c8c7434c3d0f93d4c"}}, "title": "Proteomic blood profiling in mild, severe and critical COVID-19 patients.", "authors": [{"family": "Patel", "given": "Hamel", "initials": "H", "orcid": "0000-0001-7951-6728", "researcher": {"href": "https://publications.scilifelab.se/researcher/159bd008db1c4b78b68bdc4996944f4d.json"}}, {"family": "Ashton", "given": "Nicholas J", "initials": "NJ", "orcid": "0000-0002-3579-8804", "researcher": {"href": "https://publications.scilifelab.se/researcher/5a9f8df1bf6f4c4d998e04cc806de93d.json"}}, {"family": "Dobson", "given": "Richard J B", "initials": "RJB", "orcid": "0000-0003-4224-9245", "researcher": {"href": "https://publications.scilifelab.se/researcher/098ba38a51a64ba89362ed2a2e51455f.json"}}, {"family": "Andersson", "given": "Lars-Magnus", "initials": "LM"}, {"family": "Yilmaz", "given": "Aylin", "initials": "A"}, {"family": "Blennow", "given": "Kaj", "initials": "K"}, {"family": "Gisslen", "given": "Magnus", "initials": "M"}, {"family": "Zetterberg", "given": "Henrik", "initials": "H", "orcid": "0000-0003-3930-4354", "researcher": {"href": "https://publications.scilifelab.se/researcher/85efee74eb4a4b38b63cf2823d204529.json"}}], "type": "comparative study", "published": "2021-03-18", "journal": {"title": "Sci Rep", "issn": "2045-2322", "volume": "11", "issue": "1", "pages": "6357", "issn-l": "2045-2322"}, "abstract": "The recent SARS-CoV-2 pandemic manifests itself as a mild respiratory tract infection in most individuals, leading to COVID-19 disease. However, in some infected individuals, this can progress to severe pneumonia and acute respiratory distress syndrome (ARDS), leading to multi-organ failure and death. This study explores the proteomic differences between mild, severe, and critical COVID-19 positive patients to further understand the disease progression, identify proteins associated with disease severity, and identify potential therapeutic targets. Blood protein profiling was performed on 59 COVID-19 mild (n = 26), severe (n = 9) or critical (n = 24) cases and 28 controls using the OLINK inflammation, autoimmune, cardiovascular and neurology panels. Differential expression analysis was performed within and between disease groups to generate nine different analyses. From the 368 proteins measured per individual, more than 75% were observed to be significantly perturbed in COVID-19 cases. Six proteins (IL6, CKAP4, Gal-9, IL-1ra, LILRB4 and PD-L1) were identified to be associated with disease severity. The results have been made readily available through an interactive web-based application for instant data exploration and visualization, and can be accessed at https://phidatalab-shiny.rosalind.kcl.ac.uk/COVID19/ . Our results demonstrate that dynamic changes in blood proteins associated with disease severity can potentially be used as early biomarkers to monitor disease severity in COVID-19 and serve as potential therapeutic targets.", "doi": "10.1038/s41598-021-85877-0", "pmid": "33737684", "labels": {"Affinity Proteomics Uppsala": "Service"}, "xrefs": [{"db": "pii", "key": "10.1038/s41598-021-85877-0"}, {"db": "pmc", "key": "PMC7973581"}], "notes": [], "created": "2021-12-10T09:30:03.774Z", "modified": "2021-12-10T09:30:03.901Z"}, {"entity": "publication", "iuid": "36a139ec84d74001845f829037276801", "links": {"self": {"href": "https://publications.scilifelab.se/publication/36a139ec84d74001845f829037276801.json"}, "display": {"href": "https://publications.scilifelab.se/publication/36a139ec84d74001845f829037276801"}}, "title": "Chemical imaging of evolving amyloid plaque pathology and associated A\u03b2 peptide aggregation in a transgenic mouse model of Alzheimer's disease.", "authors": [{"family": "Michno", "given": "Wojciech", "initials": "W", "orcid": "0000-0002-3096-3604", "researcher": {"href": "https://publications.scilifelab.se/researcher/7b4307eb6e45426e8176337e88c9c344.json"}}, {"family": "Wehrli", "given": "Patrick", "initials": "P"}, {"family": "Meier", "given": "Silvio R", "initials": "SR"}, {"family": "Sehlin", "given": "Dag", "initials": "D"}, {"family": "Syv\u00e4nen", "given": "Stina", "initials": "S"}, {"family": "Zetterberg", "given": "Henrik", "initials": "H", "orcid": "0000-0003-3930-4354", "researcher": {"href": "https://publications.scilifelab.se/researcher/85efee74eb4a4b38b63cf2823d204529.json"}}, {"family": "Blennow", "given": "Kaj", "initials": "K"}, {"family": "Hanrieder", "given": "J\u00f6rg", "initials": "J", "orcid": "0000-0001-6059-198X", "researcher": {"href": "https://publications.scilifelab.se/researcher/4e65454100674f98bf8f2575093f2441.json"}}], "type": "journal article", "published": "2020-03-00", "journal": {"title": "J. Neurochem.", "issn": "1471-4159", "volume": "152", "issue": "5", "pages": "602-616", "issn-l": "0022-3042"}, "abstract": "One of the major hallmarks of Alzheimer's disease (AD) pathology is the formation of extracellular amyloid \u03b2 (A\u03b2) plaques. While A\u03b2 has been suggested to be critical in inducing and, potentially, driving the disease, the molecular basis of AD pathogenesis is still under debate. Extracellular A\u03b2 plaque pathology manifests itself upon aggregation of distinct A\u03b2 peptides, resulting in morphologically different plaque morphotypes, including mainly diffuse and cored senile plaques. As plaque pathology precipitates long before any clinical symptoms occur, targeting the A\u03b2 aggregation processes provides a promising target for early interventions. However, the chain of events of when, where and what A\u03b2 species aggregate and form plaques remains unclear. The aim of this study was to investigate the potential of matrix-assisted laser desorption/ionization imaging mass spectrometry as a tool to study the evolving pathology in transgenic mouse models for AD. To that end, we used an emerging, chemical imaging modality - matrix-assisted laser desorption/ionization imaging mass spectrometry - that allows for delineating A\u03b2 aggregation with specificity at the single plaque level. We identified that plaque formation occurs first in cortical regions and that these younger plaques contain higher levels of 42 amino acid-long A\u03b2 (A\u03b21-42). Plaque maturation was found to be characterized by a relative increase in deposition of A\u03b21-40, which was associated with the appearance of a cored morphology for those plaques. Finally, other C-terminally truncated A\u03b2 species (A\u03b21-38 and A\u03b21-39) exhibited a similar aggregation pattern as A\u03b21-40, suggesting that these species have similar aggregation characteristics. These results suggest that initial plaque formation is seeded by A\u03b21-42; a process that is followed by plaque maturation upon deposition of A\u03b21-40 as well as deposition of other C-terminally modified A\u03b2 species.", "doi": "10.1111/jnc.14888", "pmid": "31605538", "labels": {"Integrated Microscopy Technologies Gothenburg": "Collaborative"}, "xrefs": [], "notes": [], "created": "2023-02-16T08:08:09.467Z", "modified": "2023-02-16T08:12:11.343Z"}]}