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The objective of this study was to use samples from this cohort to identify cerebrospinal fluid\u00a0 (CSF) biomarkers for AD\u2010related central nervous system (CNS) pathophysiologic changes using tissue and fluids with early pathology, free of <jats:italic>post mortem<\/jats:italic> artifact.<\/jats:p><\/jats:sec><jats:sec><jats:title>METHODS<\/jats:title><jats:p>We analyzed Simoa, proteomic, and metabolomic CSF data from 81 patients with previously documented pathologic and transcriptomic changes.<\/jats:p><\/jats:sec><jats:sec><jats:title>RESULTS<\/jats:title><jats:p>AD pathology on biopsy correlates with CSF \u03b2\u2010amyloid\u201042\/40, neurofilament light chain (NfL), and phospho\u2010tau\u2010181(p\u2010tau181)\/<jats:italic>\u03b2<\/jats:italic>\u2010amyloid\u201042, while several gene expression modules correlate with NfL. Proteomic analysis highlights seven core proteins that correlate with pathology and gene expression changes on biopsy, and metabolomic analysis of CSF identifies disease\u2010relevant groups that correlate with biopsy data.<\/jats:p><\/jats:sec><jats:sec><jats:title>DISCUSSION<\/jats:title><jats:p>As additional biomarkers are added to AD diagnostic panels, our work provides insight into the CNS pathophysiology these markers are tracking.<\/jats:p><\/jats:sec><jats:sec><jats:title>Highlights<\/jats:title><jats:p><jats:list list-type=\"bullet\">\n<jats:list-item><jats:p>AD CSF biomarkers correlate with CNS pathology and transcriptomic changes.<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p>Seven proteins correlate with CNS pathology and gene expression changes.<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p>Inflammatory and neuronal gene expression changes correlate with YKL\u201040 and NPTXR, respectively.<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p>CSF metabolomic analysis identifies pathways that correlate with biopsy data.<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p>Fatty acid metabolic pathways correlate with \u03b2\u2010amyloid pathology.<\/jats:p><\/jats:list-item>\n<\/jats:list><\/jats:p><\/jats:sec>","DOI":"10.1002\/alz.14194","type":"journal-article","created":{"date-parts":[[2024,8,28]],"date-time":"2024-08-28T02:13:56Z","timestamp":1724811236000},"page":"7090-7103","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["Alzheimer's disease CSF biomarkers correlate with early pathology and alterations in neuronal and glial gene expression"],"prefix":"10.1002","volume":"20","author":[{"given":"Ali S.","family":"Ropri","sequence":"first","affiliation":[{"name":"Department of Pathology and Cell Biology Columbia University Irving Medical Center  New York New York USA"},{"name":"Taub Institute for Research on Alzheimer's Disease and the Aging Brain Columbia University Irving Medical Center  New York New York USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tiffany G.","family":"Lam","sequence":"additional","affiliation":[{"name":"Department of Pathology and Cell Biology Columbia University Irving Medical Center  New York New York USA"},{"name":"Taub Institute for Research on Alzheimer's Disease and the Aging Brain Columbia University Irving Medical Center  New York New York USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vrinda","family":"Kalia","sequence":"additional","affiliation":[{"name":"Department of Environmental Health Sciences, Mailman School of Public Health Columbia University  New York New York USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Heather M.","family":"Buchanan","sequence":"additional","affiliation":[{"name":"Department of Pathology and Cell Biology Columbia University Irving Medical Center  New York New York USA"},{"name":"Taub Institute for Research on Alzheimer's Disease and the Aging Brain Columbia University Irving Medical Center  New York New York USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anne Marie W.","family":"Bartosch","sequence":"additional","affiliation":[{"name":"Department of Pathology and Cell Biology Columbia University Irving Medical Center  New York New York USA"},{"name":"Taub Institute for Research on Alzheimer's Disease and the Aging Brain Columbia University Irving Medical Center  New York New York USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elliot H. H.","family":"Youth","sequence":"additional","affiliation":[{"name":"Department of Pathology and Cell Biology Columbia University Irving Medical Center  New York New York USA"},{"name":"Taub Institute for Research on Alzheimer's Disease and the Aging Brain Columbia University Irving Medical Center  New York New York USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Harrison","family":"Xiao","sequence":"additional","affiliation":[{"name":"Department of Pathology and Cell Biology Columbia University Irving Medical Center  New York New York USA"},{"name":"Taub Institute for Research on Alzheimer's Disease and the Aging Brain Columbia University Irving Medical Center  New York New York USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sophie K.","family":"Ross","sequence":"additional","affiliation":[{"name":"Department of Pathology and Cell Biology Columbia University Irving Medical Center  New York New York USA"},{"name":"Taub Institute for Research 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