{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,7]],"date-time":"2026-11-07T04:31:28Z","timestamp":1794025888910,"version":"4.8.0"},"reference-count":48,"publisher":"American Association for the Advancement of Science (AAAS)","issue":"703","content-domain":{"domain":["www.science.org"],"crossmark-restriction":true},"short-container-title":["Sci. Transl. Med."],"published-print":{"date-parts":[[2023,7,5]]},"abstract":"<jats:p>\n                    Proteomic studies for Alzheimer\u2019s disease (AD) are instrumental in identifying AD pathways but often focus on single tissues and sporadic AD cases. Here, we present a proteomic study analyzing 1305 proteins in brain tissue, cerebrospinal fluid (CSF), and plasma from patients with sporadic AD,\n                    <jats:italic>TREM2<\/jats:italic>\n                    risk variant carriers, patients with autosomal dominant AD (ADAD), and healthy individuals. We identified 8 brain, 40 CSF, and 9 plasma proteins that were altered in individuals with sporadic AD, and we replicated these findings in several external datasets. We identified a proteomic signature that differentiated\n                    <jats:italic>TREM2<\/jats:italic>\n                    variant carriers from both individuals with sporadic AD and healthy individuals. The proteins associated with sporadic AD were also altered in patients with ADAD, but with a greater effect size. Brain-derived proteins associated with ADAD were also replicated in additional CSF samples. Enrichment analyses highlighted several pathways, including those implicated in AD (calcineurin and Apo E), Parkinson\u2019s disease (\u03b1-synuclein and LRRK2), and innate immune responses (SHC1, ERK-1, and SPP1). Our findings suggest that combined proteomics across brain tissue, CSF, and plasma can be used to identify markers for sporadic and genetically defined AD.\n                  <\/jats:p>","DOI":"10.1126\/scitranslmed.abq5923","type":"journal-article","created":{"date-parts":[[2023,7,5]],"date-time":"2023-07-05T13:58:13Z","timestamp":1688565493000},"update-policy":"https:\/\/doi.org\/10.34133\/aaas_crossmark","source":"Crossref","is-referenced-by-count":97,"title":["Proteomics of brain, CSF, and plasma identifies molecular signatures for distinguishing sporadic and genetic Alzheimer\u2019s disease"],"prefix":"10.1126","volume":"15","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-8021-4070","authenticated-orcid":true,"given":"Yun Ju","family":"Sung","sequence":"first","affiliation":[{"name":"Department of Psychiatry, Washington University School of Medicine, St.\u00a0Louis, MO 63108, USA."},{"name":"NeuroGenomics and Informatics Center, Washington University School of Medicine, St.\u00a0Louis, MO 63108, USA."},{"name":"Division of Biostatistics, Washington University School of Medicine, St.\u00a0Louis, MO 63108, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4577-5590","authenticated-orcid":true,"given":"Chengran","family":"Yang","sequence":"additional","affiliation":[{"name":"Department of Psychiatry, Washington University School of Medicine, St.\u00a0Louis, MO 63108, USA."},{"name":"NeuroGenomics and Informatics Center, Washington University School of Medicine, St.\u00a0Louis, MO 63108, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joanne","family":"Norton","sequence":"additional","affiliation":[{"name":"Department of Psychiatry, Washington University School of Medicine, St.\u00a0Louis, MO 63108, USA."},{"name":"NeuroGenomics and Informatics Center, Washington University School of Medicine, St.\u00a0Louis, MO 63108, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Matt","family":"Johnson","sequence":"additional","affiliation":[{"name":"Department of Psychiatry, Washington University School of Medicine, St.\u00a0Louis, MO 63108, USA."},{"name":"NeuroGenomics and Informatics Center, Washington University School of Medicine, St.\u00a0Louis, MO 63108, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anne","family":"Fagan","sequence":"additional","affiliation":[{"name":"Charles F.\u00a0and Joanne Knight Alzheimer Disease Research Center, Washington University School of Medicine, St.\u00a0Louis, MO 63108, USA."},{"name":"Department of Neurology, Washington University School of Medicine, St.\u00a0Louis, MO 63108, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7729-1702","authenticated-orcid":true,"given":"Randall J.","family":"Bateman","sequence":"additional","affiliation":[{"name":"Charles F.\u00a0and Joanne Knight Alzheimer Disease Research Center, Washington University School of Medicine, St.\u00a0Louis, MO 63108, USA."},{"name":"Department of Neurology, Washington University School of Medicine, St.\u00a0Louis, MO 63108, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3443-7716","authenticated-orcid":true,"given":"Richard J.","family":"Perrin","sequence":"additional","affiliation":[{"name":"Charles F.\u00a0and Joanne Knight Alzheimer Disease Research Center, Washington University School of Medicine, St.\u00a0Louis, MO 63108, USA."},{"name":"Department of Neurology, Washington University School of Medicine, St.\u00a0Louis, MO 63108, USA."},{"name":"Department of Pathology and Immunology, Washington University School of Medicine, St.\u00a0Louis, MO 63108, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9820-5618","authenticated-orcid":true,"given":"John 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