{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"institution":[{"name":"bioRxiv"}],"indexed":{"date-parts":[[2026,7,30]],"date-time":"2026-07-30T12:14:20Z","timestamp":1785413660290,"version":"3.56.0"},"posted":{"date-parts":[[2026,6,28]]},"group-title":"Neuroscience","reference-count":65,"publisher":"openRxiv","license":[{"start":{"date-parts":[[2026,6,28]],"date-time":"2026-06-28T00:00:00Z","timestamp":1782604800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/www.biorxiv.org\/about\/FAQ#license"}],"funder":[{"award":["R01AG071567"],"award-info":[{"award-number":["R01AG071567"]}],"id":[{"id":"https:\/\/ror.org\/01cwqze88","id-type":"ROR","asserted-by":"publisher"}]},{"award":["P30AG062421"],"award-info":[{"award-number":["P30AG062421"]}],"id":[{"id":"https:\/\/ror.org\/01cwqze88","id-type":"ROR","asserted-by":"publisher"}]},{"DOI":"10.13039\/100012513","name":"Coins for Alzheimer's Research Trust","doi-asserted-by":"crossref","id":[{"id":"10.13039\/100012513","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"accepted":{"date-parts":[[2026,6,28]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                <jats:p>\n                  Cerebrovascular alterations are widely observed in both Alzheimer\u2019s Disease (AD) and primary tauopathies. Here, we hypothesized that mechanisms of cerebrovascular alterations are shared between AD and primary tauopathies. We performed single-nucleus RNA sequencing of\n                  <jats:italic>postmortem<\/jats:italic>\n                  human inferior temporal gyrus to characterize transcriptomic changes across cerebrovascular cell types in AD and primary tauopathies (Corticobasal Degeneration, Pick\u2019s disease, and Progressive Supranuclear Palsy). Differential gene expression analyses revealed disease-specific transcriptional programs across vascular cell populations. However, genes involved in the heat-shock response were consistently upregulated across all diseases, suggesting a conserved cerebrovascular stress response during neurodegeneration. We further identified marked cerebrovascular remodeling in AD relative to primary tauopathies, along with dysregulation of genes mapping to AD risk loci in endothelial cells. Transcriptomic findings were validated using tissue clearing, light-sheet microscopy, and immunofluorescence quantification of vascular markers. These results define a conserved vascular stress program alongside AD-specific remodeling, highlighting the vasculature as a therapeutic target in neurodegeneration.\n                <\/jats:p>","DOI":"10.64898\/2026.06.26.734052","type":"posted-content","created":{"date-parts":[[2026,6,28]],"date-time":"2026-06-28T10:20:17Z","timestamp":1782642017000},"source":"Crossref","is-referenced-by-count":0,"title":["Cerebrovascular Single-Nucleus RNA-Seq Reveals Heat Shock Activation and Vascular Remodeling in Alzheimer\u2019s Disease and Primary Tauopathies"],"prefix":"10.64898","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-8521-8978","authenticated-orcid":false,"given":"LD","family":"Estrella","sequence":"first","affiliation":[{"name":"Department of Neurology, Harvard Medical School, MassGeneral Institute for Neurodegenerative Disease, Massachusetts General Hospital, Charlestown, Massachusetts 02129 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