{"entity": "researcher", "timestamp": "2026-08-07T19:24:53.059Z", "family": "Gobom", "given": "Johan", "initials": "J", "orcid": "0000-0001-6193-6193", "affiliations": ["Department of Psychiatry and Neurochemistry, Institute of Neuroscience and Physiology, Sahlgrenska Academy at University of Gothenburg, M\u00f6lndal, Sweden.", "Clinical Neurochemistry Laboratory, Sahlgrenska University Hospital, M\u00f6lndal, Sweden."], "links": {"self": {"href": "https://publications.scilifelab.se/researcher/add4c0c68cff447383c1f0184e2be943.json"}, "display": {"href": "https://publications.scilifelab.se/researcher/add4c0c68cff447383c1f0184e2be943"}}, "publications": [{"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": "aeb04606dd804999ad7eeda50801fa80", "links": {"self": {"href": "https://publications.scilifelab.se/publication/aeb04606dd804999ad7eeda50801fa80.json"}, "display": {"href": "https://publications.scilifelab.se/publication/aeb04606dd804999ad7eeda50801fa80"}}, "title": "Somatic CAG repeat expansion in blood associates with biomarkers of neurodegeneration in Huntington's disease decades before clinical motor diagnosis.", "authors": [{"family": "Scahill", "given": "Rachael I", "initials": "RI"}, {"family": "Farag", "given": "Mena", "initials": "M", "orcid": "0000-0002-0679-0117", "researcher": {"href": "https://publications.scilifelab.se/researcher/e80e5f0ebb00498f8dbf2fb4518e459a.json"}}, {"family": "Murphy", "given": "Michael J", "initials": "MJ"}, {"family": "Hobbs", "given": "Nicola Z", "initials": "NZ"}, {"family": "Leocadi", "given": "Michela", "initials": "M"}, {"family": "Langley", "given": "Christelle", "initials": "C", "orcid": "0000-0001-5061-2820", "researcher": {"href": "https://publications.scilifelab.se/researcher/f12932ef6d674608b4da04d09836770c.json"}}, {"family": "Knights", "given": "Harry", "initials": "H"}, {"family": "Ciosi", "given": "Marc", "initials": "M", "orcid": "0000-0002-7663-4080", "researcher": {"href": "https://publications.scilifelab.se/researcher/11d89a99b658483ea65d11c2f0af96c1.json"}}, {"family": "Fayer", "given": "Kate", "initials": "K"}, {"family": "Nakajima", "given": "Mitsuko", "initials": "M"}, {"family": "Thackeray", "given": "Olivia", "initials": "O"}, {"family": "Gobom", "given": "Johan", "initials": "J", "orcid": "0000-0001-6193-6193", "researcher": {"href": "https://publications.scilifelab.se/researcher/add4c0c68cff447383c1f0184e2be943.json"}}, {"family": "R\u00f6nnholm", "given": "John", "initials": "J"}, {"family": "Weiner", "given": "Sophia", "initials": "S", "orcid": "0009-0000-2298-220X", "researcher": {"href": "https://publications.scilifelab.se/researcher/501cabeaaa3649ffa111f9c445065fed.json"}}, {"family": "Hassan", "given": "Yara R", "initials": "YR"}, {"family": "Ponraj", "given": "Nehaa K P", "initials": "NKP", "orcid": "0009-0002-9576-5753", "researcher": {"href": "https://publications.scilifelab.se/researcher/c15cb959adaa4dd69f9fcfecfde82336.json"}}, {"family": "Estevez-Fraga", "given": "Carlos", "initials": "C", "orcid": "0000-0001-6855-1093", "researcher": {"href": "https://publications.scilifelab.se/researcher/a358aae32ce141f081748a37bc1d361c.json"}}, {"family": "Parker", "given": "Christopher S", "initials": "CS"}, {"family": "Malone", "given": "Ian B", "initials": "IB"}, {"family": "Hyare", "given": "Harpreet", "initials": "H"}, {"family": "Long", "given": "Jeffrey D", "initials": "JD", "orcid": "0000-0001-7181-9652", "researcher": {"href": "https://publications.scilifelab.se/researcher/9cbb5cdb954a4f0ea50cb27c0ffd31ed.json"}}, {"family": "Heslegrave", "given": "Amanda", "initials": "A"}, {"family": "Sampaio", "given": "Cristina", "initials": "C", "orcid": "0000-0002-7052-9079", "researcher": {"href": "https://publications.scilifelab.se/researcher/e977513b61bf47b5a81489c74ad612e4.json"}}, {"family": "Zhang", "given": "Hui", "initials": "H", "orcid": "0000-0002-5426-2140", "researcher": {"href": "https://publications.scilifelab.se/researcher/b4da907c8afe4858b02b4914520bcf5b.json"}}, {"family": "Robbins", "given": "Trevor W", "initials": "TW", "orcid": "0000-0003-0642-5977", "researcher": {"href": "https://publications.scilifelab.se/researcher/9accce3ce1c54ce18f8557dedc1dbf15.json"}}, {"family": "Zetterberg", "given": "Henrik", "initials": "H"}, {"family": "Wild", "given": "Edward J", "initials": "EJ", "orcid": "0000-0002-6921-7887", "researcher": {"href": "https://publications.scilifelab.se/researcher/25781990d57a455c8a5e2332669cea0b.json"}}, {"family": "Rees", "given": "Geraint", "initials": "G", "orcid": "0000-0002-9623-7007", "researcher": {"href": "https://publications.scilifelab.se/researcher/dfba7a08558246cdb7259d79344a4f80.json"}}, {"family": "Rowe", "given": "James B", "initials": "JB", "orcid": "0000-0001-7216-8679", "researcher": {"href": "https://publications.scilifelab.se/researcher/4211255a53fd4ce5a2903f8b3fa75dcb.json"}}, {"family": "Sahakian", "given": "Barbara J", "initials": "BJ", "orcid": "0000-0001-7352-1745", "researcher": {"href": "https://publications.scilifelab.se/researcher/522cd4149c914cd19da7e78852526bbd.json"}}, {"family": "Monckton", "given": "Darren G", "initials": "DG", "orcid": "0000-0002-8298-8264", "researcher": {"href": "https://publications.scilifelab.se/researcher/a982cf9a4bf946c497765c5953230788.json"}}, {"family": "Langbehn", "given": "Douglas R", "initials": "DR"}, {"family": "Tabrizi", "given": "Sarah J", "initials": "SJ", "orcid": "0000-0003-2716-2045", "researcher": {"href": "https://publications.scilifelab.se/researcher/1b5169e345e3411587abd10613f57d1d.json"}}], "type": "journal article", "published": "2025-03-00", "journal": {"title": "Nat. Med.", "issn": "1546-170X", "volume": "31", "issue": "3", "pages": "807-818", "issn-l": "1078-8956"}, "abstract": "Huntington's disease (HD) is an autosomal dominant neurodegenerative disease with the age at which characteristic symptoms manifest strongly influenced by inherited HTT CAG length. Somatic CAG expansion occurs throughout life and understanding the impact of somatic expansion on neurodegeneration is key to developing therapeutic targets. In 57 HD gene expanded (HDGE) individuals, ~23 years before their predicted clinical motor diagnosis, no significant decline in clinical, cognitive or neuropsychiatric function was observed over 4.5 years compared with 46 controls (false discovery rate (FDR) > 0.3). However, cerebrospinal fluid (CSF) markers showed very early signs of neurodegeneration in HDGE with elevated neurofilament light (NfL) protein, an indicator of neuroaxonal damage (FDR = 3.2 \u00d7 10-12), and reduced proenkephalin (PENK), a surrogate marker for the state of striatal medium spiny neurons (FDR = 2.6 \u00d7 10-3), accompanied by brain atrophy, predominantly in the caudate (FDR = 5.5 \u00d7 10-10) and putamen (FDR = 1.2 \u00d7 10-9). Longitudinal increase in somatic CAG repeat expansion ratio (SER) in blood was a significant predictor of subsequent caudate (FDR = 0.072) and putamen (FDR = 0.148) atrophy. Atypical loss of interruption HTT repeat structures, known to predict earlier age at clinical motor diagnosis, was associated with substantially faster caudate and putamen atrophy. We provide evidence in living humans that the influence of CAG length on HD neuropathology is mediated by somatic CAG repeat expansion. These critical mechanistic insights into the earliest neurodegenerative changes will inform the design of preventative clinical trials aimed at modulating somatic expansion. ClinicalTrials.gov registration: NCT06391619 .", "doi": "10.1038/s41591-024-03424-6", "pmid": "39825149", "labels": {"Glycoproteomics and MS Proteomics": "Service"}, "xrefs": [{"db": "pmc", "key": "PMC11922752"}, {"db": "pii", "key": "10.1038/s41591-024-03424-6"}, {"db": "ClinicalTrials.gov", "key": "NCT06391619"}], "notes": [], "created": "2025-02-11T14:14:37.115Z", "modified": "2025-11-20T17:41:58.894Z"}]}