{"entity": "researcher", "timestamp": "2026-06-17T04:13:28.889Z", "family": "Blennow", "given": "Kaj", "initials": "K", "orcid": "0000-0002-1890-4193", "affiliations": [], "links": {"self": {"href": "https://publications.scilifelab.se/researcher/5e646be026ce42ecbfd4d62eca3f9bce.json"}, "display": {"href": "https://publications.scilifelab.se/researcher/5e646be026ce42ecbfd4d62eca3f9bce"}}, "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": "2932e719620c4500849314bed605e7f7", "links": {"self": {"href": "https://publications.scilifelab.se/publication/2932e719620c4500849314bed605e7f7.json"}, "display": {"href": "https://publications.scilifelab.se/publication/2932e719620c4500849314bed605e7f7"}}, "title": "Neuroinflammation and Alzheimer's Disease: A Machine Learning Approach to CSF Proteomics.", "authors": [{"family": "Gaetani", "given": "Lorenzo", "initials": "L", "orcid": "0000-0003-3967-8954", "researcher": {"href": "https://publications.scilifelab.se/researcher/dcd83059b10746efb3d5a0263f0e68d8.json"}}, {"family": "Bellomo", "given": "Giovanni", "initials": "G", "orcid": "0000-0003-0456-5650", "researcher": {"href": "https://publications.scilifelab.se/researcher/07c5cc0baad64958aea57184a532d039.json"}}, {"family": "Parnetti", "given": "Lucilla", "initials": "L", "orcid": "0000-0001-5722-3967", "researcher": {"href": "https://publications.scilifelab.se/researcher/250f5d2b849845d384e5856b2dae56e6.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"}, {"family": "Di Filippo", "given": "Massimiliano", "initials": "M"}], "type": "journal article", "published": "2021-07-29", "journal": {"title": "Cells", "issn": "2073-4409", "volume": "10", "issue": "8", "issn-l": "2073-4409"}, "abstract": "In Alzheimer's disease (AD), the contribution of pathophysiological mechanisms other than amyloidosis and tauopathy is now widely recognized, although not clearly quantifiable by means of fluid biomarkers. We aimed to identify quantifiable protein biomarkers reflecting neuroinflammation in AD using multiplex proximity extension assay (PEA) testing. Cerebrospinal fluid (CSF) samples from patients with mild cognitive impairment due to AD (AD-MCI) and from controls, i.e., patients with other neurological diseases (OND), were analyzed with the Olink Inflammation PEA biomarker panel. A machine-learning approach was then used to identify biomarkers discriminating AD-MCI (n: 34) from OND (n: 25). On univariate analysis, SIRT2, HGF, MMP-10, and CXCL5 showed high discriminatory performance (AUC 0.809, p = 5.2 \u00d7 10-4, AUC 0.802, p = 6.4 \u00d7 10-4, AUC 0.793, p = 3.2 \u00d7 10-3, AUC 0.761, p = 2.3 \u00d7 10-3, respectively), with higher CSF levels in AD-MCI patients as compared to controls. These same proteins were the best contributors to the penalized logistic regression model discriminating AD-MCI from controls (AUC of the model 0.906, p = 2.97 \u00d7 10-7). The biological processes regulated by these proteins include astrocyte and microglia activation, amyloid, and tau misfolding modulation, and blood-brain barrier dysfunction. Using a high-throughput multiplex CSF analysis coupled with a machine-learning statistical approach, we identified novel biomarkers reflecting neuroinflammation in AD. Studies confirming these results by means of different assays are needed to validate PEA as a multiplex technique for CSF analysis and biomarker discovery in the field of neurological diseases.", "doi": "10.3390/cells10081930", "pmid": "34440700", "labels": {"Affinity Proteomics Uppsala": "Service"}, "xrefs": [{"db": "pii", "key": "cells10081930"}, {"db": "pmc", "key": "PMC8391540"}], "notes": [], "created": "2021-12-10T09:06:18.332Z", "modified": "2021-12-10T09:06:18.472Z"}, {"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": "https://publications.scilifelab.se/publication/b70be864396f40b68d30939cc4e01962.json"}, "display": {"href": "https://publications.scilifelab.se/publication/b70be864396f40b68d30939cc4e01962"}}, "title": "Common variants in Alzheimer's disease and risk stratification by polygenic risk scores.", "authors": [{"family": "de Rojas", "given": "Itziar", "initials": "I", "orcid": "0000-0002-2148-381X", "researcher": {"href": "https://publications.scilifelab.se/researcher/c4452ee79e504a9fb358068cfa6abbde.json"}}, {"family": "Moreno-Grau", "given": "Sonia", "initials": "S"}, {"family": "Tesi", "given": "Niccolo", "initials": "N"}, {"family": "Grenier-Boley", "given": "Benjamin", "initials": "B"}, {"family": "Andrade", "given": "Victor", "initials": "V"}, {"family": "Jansen", "given": "Iris E", "initials": "IE"}, {"family": "Pedersen", "given": "Nancy L", "initials": "NL"}, {"family": "Stringa", "given": "Najada", "initials": "N", "orcid": "0000-0001-6350-452X", "researcher": {"href": "https://publications.scilifelab.se/researcher/d286e52366c942c4a9f0eec9e07a7596.json"}}, {"family": "Zettergren", "given": "Anna", "initials": "A", "orcid": "0000-0002-7182-8417", "researcher": {"href": "https://publications.scilifelab.se/researcher/238188e1165e4de88918f024e3b1289e.json"}}, {"family": "Hern\u00e1ndez", "given": "Isabel", "initials": "I"}, {"family": "Montrreal", "given": "Laura", "initials": "L"}, {"family": "Ant\u00fanez", "given": "Carmen", "initials": "C"}, {"family": "Antonell", "given": "Anna", "initials": "A"}, {"family": "Tankard", "given": "Rick M", "initials": "RM", "orcid": "0000-0002-8847-9401", "researcher": {"href": "https://publications.scilifelab.se/researcher/5c109642be2b44aabfd7d210a47f6c27.json"}}, {"family": "Bis", "given": "Joshua C", "initials": "JC"}, {"family": "Sims", "given": "Rebecca", "initials": "R", "orcid": "0000-0002-3885-1199", "researcher": {"href": "https://publications.scilifelab.se/researcher/3e10b941ee2a4aa19711c68f582f00a5.json"}}, {"family": "Bellenguez", "given": "C\u00e9line", "initials": "C", "orcid": "0000-0002-1240-7874", "researcher": 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"Alberto", "initials": "A"}, {"family": "Padovani", "given": "Alessandro", "initials": "A"}, {"family": "Squassina", "given": "Alessio", "initials": "A", "orcid": "0000-0001-7415-7607", "researcher": {"href": "https://publications.scilifelab.se/researcher/dd1923e08ab1483e8eb080f4de163872.json"}}, {"family": "de Mendon\u00e7a", "given": "Alexandre", "initials": "A"}, {"family": "Arias Pastor", "given": "Alfonso", "initials": "A"}, {"family": "Kok", "given": "Almar A L", "initials": "AAL"}, {"family": "Meggy", "given": "Alun", "initials": "A"}, {"family": "Pastor", "given": "Ana Bel\u00e9n", "initials": "AB", "orcid": "0000-0001-9637-4688", "researcher": {"href": "https://publications.scilifelab.se/researcher/657703cdc796484aa3b20a41fef742c9.json"}}, {"family": "Espinosa", "given": "Ana", "initials": "A"}, {"family": "Corma-G\u00f3mez", "given": "Ana\u00efs", "initials": "A"}, {"family": "Mart\u00edn Montes", "given": "Angel", "initials": "A", "orcid": "0000-0002-1694-786X", "researcher": {"href": "https://publications.scilifelab.se/researcher/0e1090b36c484d5089aaacd50413a212.json"}}, {"family": "Sanabria", "given": "\u00c1ngela", "initials": "\u00c1"}, {"family": "DeStefano", "given": "Anita L", "initials": "AL"}, {"family": "Schneider", "given": "Anja", "initials": "A"}, {"family": "Haapasalo", "given": "Annakaisa", "initials": "A", "orcid": "0000-0003-0959-2957", "researcher": {"href": "https://publications.scilifelab.se/researcher/7c6d55489d2f41c3be4e217677d816ad.json"}}, {"family": "Kinhult St\u00e5hlbom", "given": "Anne", "initials": "A"}, {"family": "Tybj\u00e6rg-Hansen", "given": "Anne", "initials": "A"}, {"family": "Hartmann", "given": "Annette M", "initials": "AM"}, {"family": "Spottke", "given": "Annika", "initials": "A"}, {"family": "Corbat\u00f3n-Anchuelo", "given": "Arturo", "initials": "A"}, {"family": "Rongve", "given": "Arvid", "initials": "A", "orcid": "0000-0002-0476-4134", "researcher": {"href": 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"Carmen", "initials": "C"}, {"family": "Dufouil", "given": "Carole", "initials": "C"}, {"family": "Graff", "given": "Caroline", "initials": "C"}, {"family": "Ferreira", "given": "Catarina B", "initials": "CB"}, {"family": "Chillotti", "given": "Caterina", "initials": "C"}, {"family": "Reynolds", "given": "Chandra A", "initials": "CA", "orcid": "0000-0001-6502-7173", "researcher": {"href": "https://publications.scilifelab.se/researcher/6b7cd2b82d81463c8dd3f13c4d75ab6f.json"}}, {"family": "Fenoglio", "given": "Chiara", "initials": "C"}, {"family": "Van Broeckhoven", "given": "Christine", "initials": "C", "orcid": "0000-0003-0183-7665", "researcher": {"href": "https://publications.scilifelab.se/researcher/7eea44cb294a4282979f29eb0388a006.json"}}, {"family": "Clark", "given": "Christopher", "initials": "C", "orcid": "0000-0001-7210-7702", "researcher": {"href": "https://publications.scilifelab.se/researcher/2b94462467da4a16a78c4d9f4b18af01.json"}}, {"family": "Pisanu", "given": "Claudia", "initials": "C", "orcid": "0000-0002-9151-4319", "researcher": {"href": "https://publications.scilifelab.se/researcher/dcf58ed0ff0a4bac97982a5adc2ef340.json"}}, {"family": "Satizabal", "given": "Claudia L", "initials": "CL", "orcid": "0000-0002-1115-4430", "researcher": {"href": "https://publications.scilifelab.se/researcher/4fef87b562c74168ba8b9acbc9048eb9.json"}}, {"family": "Holmes", "given": "Clive", "initials": "C"}, {"family": "Buiza-Rueda", "given": "Dolores", "initials": "D"}, {"family": "Aarsland", "given": "Dag", "initials": "D", "orcid": "0000-0001-6314-216X", "researcher": {"href": "https://publications.scilifelab.se/researcher/121af6702db54d68b1ca94e8c22a8688.json"}}, {"family": "Rujescu", "given": "Dan", "initials": "D"}, {"family": "Alcolea", "given": "Daniel", "initials": "D", "orcid": "0000-0002-3819-3245", "researcher": {"href": "https://publications.scilifelab.se/researcher/57c67b243f6a4ea38023ea8ae4f35e88.json"}}, {"family": "Galimberti", "given": "Daniela", 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{"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"}]}