{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"institution":[{"name":"bioRxiv"}],"indexed":{"date-parts":[[2026,9,11]],"date-time":"2026-09-11T23:53:00Z","timestamp":1789170780425,"version":"build-2803163510"},"posted":{"date-parts":[[2025,11,25]]},"group-title":"Genomics","reference-count":52,"publisher":"openRxiv","license":[{"start":{"date-parts":[[2025,11,25]],"date-time":"2025-11-25T00:00:00Z","timestamp":1764028800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/www.biorxiv.org\/about\/FAQ#license"}],"funder":[{"DOI":"10.13039\/100000049","name":"National Institute on Aging","doi-asserted-by":"crossref","award":["R01AG079223"],"award-info":[{"award-number":["R01AG079223"]}],"id":[{"id":"10.13039\/100000049","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/100000049","name":"National Institute on Aging","doi-asserted-by":"crossref","award":["R01AG074082"],"award-info":[{"award-number":["R01AG074082"]}],"id":[{"id":"10.13039\/100000049","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"accepted":{"date-parts":[[2025,12,17]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                <jats:p>The choroid plexus (CP) regulates barrier integrity, cerebrospinal-fluid (CSF) dynamics, and immune surveillance, yet its role in Alzheimer\u2019s disease (AD) remains poorly defined. We performed snRNA-seq on CP samples from 69 ROSMAP participants spanning normal cognition, mild cognitive impairment, and AD dementia, and integrated these data with spatial transcriptomics, snATAC-seq, and proteomics from CP tissue and CSF. We identified 17 CP cell states and uncovered widespread disease-associated transitions that converged into three major phenotypic axes. Along the inflammatory axis, epithelial cells and border-associated macrophages (BAMs) showed progressive immune activation, with BAMs shifting from inflammatory to stress-dominant states. In the barrier axis, epithelial cells, fibroblasts, and endothelial cells exhibited reduced junction-related gene expression and broad alterations in transport pathways. Epithelial cells also showed late-stage cilia loss and CSF-regulatory pathway impairment, indicating a breakdown in epithelial polarity and CSF sensing, consistent with abnormal CSF proteomic signatures. Along the remodeling axis, fibroblasts showed ECM alterations, while epithelial and stromal cells demonstrated aberrant cell\u2013matrix adhesion pathways. Spatial neighborhood analysis revealed a multicellular signaling hub, with epithelial-rich niches showing the strongest dysregulation in AD. Together, these findings define a unified model of CP dysfunction in AD and position the CP as an active, multicellular contributor to AD pathophysiology.<\/jats:p>","DOI":"10.1101\/2025.11.23.690014","type":"posted-content","created":{"date-parts":[[2025,11,26]],"date-time":"2025-11-26T15:20:11Z","timestamp":1764170411000},"source":"Crossref","is-referenced-by-count":6,"title":["A Multi-omic Atlas of Human Choroid Plexus in Alzheimer\u2019s Disease"],"prefix":"10.64898","author":[{"given":"Tristan J.","family":"Philippe","sequence":"first","affiliation":[{"name":"Rush Alzheimer\u2019s Disease Center, Rush University Medical Center, Chicago, IL, 60612, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Denis R.","family":"Avey","sequence":"additional","affiliation":[{"name":"Rush Alzheimer\u2019s Disease Center, Rush University Medical Center, Chicago, IL, 60612, USA"},{"name":"Department of Neurological Sciences, Rush University Medical Center, Chicago, IL, 60612, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nicola A.","family":"Kearns","sequence":"additional","affiliation":[{"name":"Rush Alzheimer\u2019s Disease Center, Rush University Medical Center, Chicago, IL, 60612, USA"},{"name":"Department of Neurological Sciences, Rush University Medical Center, Chicago, IL, 60612, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Himanshu","family":"Vyas","sequence":"additional","affiliation":[{"name":"Rush Alzheimer\u2019s Disease Center, Rush University Medical Center, Chicago, IL, 60612, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sashini De","family":"Tissera","sequence":"additional","affiliation":[{"name":"Rush Alzheimer\u2019s Disease Center, Rush University Medical Center, Chicago, IL, 60612, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jishu","family":"Xu","sequence":"additional","affiliation":[{"name":"Rush Alzheimer\u2019s Disease Center, Rush University Medical Center, Chicago, IL, 60612, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bernard","family":"Ng","sequence":"additional","affiliation":[{"name":"Rush Alzheimer\u2019s Disease Center, Rush University Medical Center, Chicago, IL, 60612, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Devin M.","family":"Saunders","sequence":"additional","affiliation":[{"name":"Rush Alzheimer\u2019s Disease Center, Rush University Medical Center, Chicago, IL, 60612, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Amiko K.","family":"Lagrimas","sequence":"additional","affiliation":[{"name":"Rush Alzheimer\u2019s Disease Center, Rush University Medical Center, Chicago, IL, 60612, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Duc","family":"Duong","sequence":"additional","affiliation":[{"name":"Emory University School of Medicine, Atlanta, GA 30322, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nicholas T.","family":"Seyfried","sequence":"additional","affiliation":[{"name":"Emory University School of Medicine, Atlanta, GA 30322, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David A.","family":"Bennett","sequence":"additional","affiliation":[{"name":"Rush Alzheimer\u2019s Disease Center, Rush University Medical Center, Chicago, IL, 60612, USA"},{"name":"Department of Neurological Sciences, Rush University Medical Center, Chicago, IL, 60612, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8589-4239","authenticated-orcid":false,"given":"Yanling","family":"Wang","sequence":"additional","affiliation":[{"name":"Rush Alzheimer\u2019s Disease Center, Rush University Medical Center, Chicago, IL, 60612, USA"},{"name":"Department of Neurological Sciences, Rush University Medical Center, Chicago, IL, 60612, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"54368","reference":[{"key":"2026010105431726000_2025.11.23.690014v2.1","doi-asserted-by":"publisher","DOI":"10.1152\/physrev.00060.2021"},{"key":"2026010105431726000_2025.11.23.690014v2.2","doi-asserted-by":"publisher","DOI":"10.1101\/2024.07.08.601696"},{"key":"2026010105431726000_2025.11.23.690014v2.3","doi-asserted-by":"crossref","first-page":"224","DOI":"10.3390\/biomedicines10020224","article-title":"Choroid plexus in Alzheimer\u2019s disease-the current state of knowledge","volume":"10","year":"2022","journal-title":"Biomedicines"},{"key":"2026010105431726000_2025.11.23.690014v2.4","doi-asserted-by":"publisher","DOI":"10.1152\/physrev.00031.2020"},{"key":"2026010105431726000_2025.11.23.690014v2.5","doi-asserted-by":"crossref","first-page":"87","DOI":"10.3389\/fnagi.2019.00087","article-title":"Decreased cerebrospinal fluid flow is associated with cognitive deficit in elderly patients","volume":"11","year":"2019","journal-title":"Front. 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