{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,19]],"date-time":"2026-10-19T23:09:03Z","timestamp":1792451343567,"version":"4.5.0"},"reference-count":65,"publisher":"Society for Neuroscience","issue":"24","license":[{"start":{"date-parts":[[2023,12,14]],"date-time":"2023-12-14T00:00:00Z","timestamp":1702512000000},"content-version":"vor","delay-in-days":209,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc-sa\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000049","name":"HHS | NIH | National Institute on Aging","doi-asserted-by":"publisher","award":["R01AG071567"],"award-info":[{"award-number":["R01AG071567"]}],"id":[{"id":"10.13039\/100000049","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000049","name":"HHS | NIH | National Institute on Aging","doi-asserted-by":"publisher","award":["P30AG062421"],"award-info":[{"award-number":["P30AG062421"]}],"id":[{"id":"10.13039\/100000049","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000049","name":"HHS | NIH | National Institute on Aging","doi-asserted-by":"publisher","award":["K08AG064039"],"award-info":[{"award-number":["K08AG064039"]}],"id":[{"id":"10.13039\/100000049","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["J. Neurosci."],"accepted":{"date-parts":[[2023,5,11]]},"published-print":{"date-parts":[[2023,6,14]]},"abstract":"<jats:p>Vascular endothelial cells play an important role in maintaining brain health, but their contribution to Alzheimer's disease (AD) is obscured by limited understanding of the cellular heterogeneity in normal aged brain and in disease. To address this, we performed single nucleus RNAseq on tissue from 32 human AD and non-AD donors (19 female, 13 male) each with five cortical regions: entorhinal cortex, inferior temporal gyrus, prefrontal cortex, visual association cortex, and primary visual cortex. Analysis of 51,586 endothelial cells revealed unique gene expression patterns across the five regions in non-AD donors. Alzheimer's brain endothelial cells were characterized by upregulated protein folding genes and distinct transcriptomic differences in response to amyloid \u03b2 plaques and cerebral amyloid angiopathy. This dataset demonstrates previously unrecognized regional heterogeneity in the endothelial cell transcriptome in both aged non-AD and AD brain.<\/jats:p>\n                  <jats:p>\n                    <jats:bold>SIGNIFICANCE STATEMENT<\/jats:bold>\n                    In this work, we show that vascular endothelial cells collected from five different brain regions display surprising variability in gene expression. In the presence of Alzheimer's disease pathology, endothelial cell gene expression is dramatically altered with clear differences in regional and temporal changes. These findings help explain why certain brain regions appear to differ in susceptibility to disease-related vascular remodeling events that may impact blood flow.\n                  <\/jats:p>","DOI":"10.1523\/jneurosci.0237-23.2023","type":"journal-article","created":{"date-parts":[[2023,5,19]],"date-time":"2023-05-19T13:50:27Z","timestamp":1684504227000},"page":"4541-4557","source":"Crossref","is-referenced-by-count":82,"title":["Endothelial Cells Are Heterogeneous in Different Brain Regions and Are Dramatically Altered in Alzheimer's Disease"],"prefix":"10.1523","volume":"43","author":[{"given":"Annie","family":"Bryant","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhaozhi","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rojashree","family":"Jayakumar","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alberto","family":"Serrano-Pozo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Benjamin","family":"Woost","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Miwei","family":"Hu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maya E.","family":"Woodbury","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Astrid","family":"Wachter","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gen","family":"Lin","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Taekyung","family":"Kwon","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Robert V.","family":"Talanian","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Knut","family":"Biber","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eric H.","family":"Karran","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bradley T.","family":"Hyman","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sudeshna","family":"Das","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rachel E.","family":"Bennett","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"393","published-online":{"date-parts":[[2023,5,19]]},"reference":[{"key":"2024090911401085000_43.24.4541.1","unstructured":"Alzheimer DataLENS (2023) https:\/\/alzdatalens.partners.org\/?page=sample-level. Accessed February 10, 2023."},{"key":"2024090911401085000_43.24.4541.2","doi-asserted-by":"publisher","DOI":"10.1212\/WNL.42.3.631"},{"key":"2024090911401085000_43.24.4541.3","doi-asserted-by":"crossref","first-page":"25","DOI":"10.1038\/75556","article-title":"Gene ontology: tool for the unification of biology. The Gene Ontology Consortium","volume":"25","author":"Ashburner","year":"2021","journal-title":"Nat Genet"},{"key":"2024090911401085000_43.24.4541.4","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-019-14198-8"},{"key":"2024090911401085000_43.24.4541.5","doi-asserted-by":"publisher","DOI":"10.1007\/s00330-016-4450-z"},{"key":"2024090911401085000_43.24.4541.6","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1710329115"},{"key":"2024090911401085000_43.24.4541.7","doi-asserted-by":"crossref","first-page":"234","DOI":"10.3389\/fncel.2021.696540","article-title":"Location matters: navigating regional heterogeneity of the neurovascular unit","volume":"15","author":"Bernier","year":"2021","journal-title":"Front Cell Neurosci"},{"key":"2024090911401085000_43.24.4541.8","doi-asserted-by":"publisher","DOI":"10.1517\/14728222.2014.943185"},{"key":"2024090911401085000_43.24.4541.9","doi-asserted-by":"publisher","DOI":"10.1007\/BF00308809"},{"key":"2024090911401085000_43.24.4541.10","doi-asserted-by":"publisher","DOI":"10.1007\/s00401-006-0127-z"},{"key":"2024090911401085000_43.24.4541.11","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2990.2010.01139.x"},{"key":"2024090911401085000_43.24.4541.12","doi-asserted-by":"crossref","first-page":"575953","DOI":"10.3389\/fneur.2020.575953","article-title":"Cerebrovascular senescence is associated with tau pathology in Alzheimer's disease","volume":"11","author":"Bryant","year":"2020","journal-title":"Front Neurol"},{"key":"2024090911401085000_43.24.4541.13","doi-asserted-by":"publisher","DOI":"10.1093\/brain\/awx047"},{"key":"2024090911401085000_43.24.4541.14","doi-asserted-by":"publisher","DOI":"10.1016\/j.celrep.2020.03.012"},{"key":"2024090911401085000_43.24.4541.15","doi-asserted-by":"crossref","first-page":"1107","DOI":"10.1038\/s43587-021-00142-3","article-title":"Profiling senescent cells in human brains reveals neurons with CDKN2D\/p19 and tau neuropathology","volume":"1","author":"Dehkordi","year":"2021","journal-title":"Nat Aging"},{"key":"2024090911401085000_43.24.4541.16","doi-asserted-by":"publisher","DOI":"10.1016\/0361-9230(81)90007-1"},{"key":"2024090911401085000_43.24.4541.17","doi-asserted-by":"publisher","DOI":"10.1186\/s13059-014-0572-2"},{"key":"2024090911401085000_43.24.4541.18","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gkaa1113"},{"key":"2024090911401085000_43.24.4541.19","doi-asserted-by":"publisher","DOI":"10.1007\/s00401-021-02263-w"},{"key":"2024090911401085000_43.24.4541.20","doi-asserted-by":"publisher","DOI":"10.1002\/ana.410410106"},{"key":"2024090911401085000_43.24.4541.21","doi-asserted-by":"publisher","DOI":"10.1038\/ng.440"},{"key":"2024090911401085000_43.24.4541.22","doi-asserted-by":"publisher","DOI":"10.1001\/archneur.55.9.1185"},{"key":"2024090911401085000_43.24.4541.23","doi-asserted-by":"publisher","DOI":"10.1038\/s41593-021-00905-6"},{"key":"2024090911401085000_43.24.4541.24","doi-asserted-by":"publisher","DOI":"10.1038\/sdata.2018.160"},{"key":"2024090911401085000_43.24.4541.25","doi-asserted-by":"publisher","DOI":"10.1161\/01.ATV.20.3.617"},{"key":"2024090911401085000_43.24.4541.26","doi-asserted-by":"publisher","DOI":"10.1038\/s41586-019-1506-7"},{"key":"2024090911401085000_43.24.4541.27","doi-asserted-by":"publisher","DOI":"10.1016\/j.jalz.2011.10.007"},{"key":"2024090911401085000_43.24.4541.28","doi-asserted-by":"publisher","DOI":"10.1038\/ncomms11934"},{"key":"2024090911401085000_43.24.4541.29","doi-asserted-by":"crossref","first-page":"e51413","DOI":"10.7554\/eLife.51413","article-title":"Endothelial heterogeneity across distinct vascular beds during homeostasis and inflammation","volume":"9","author":"Jambusaria","year":"2020","journal-title":"Elife"},{"key":"2024090911401085000_43.24.4541.30","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2020.01.015"},{"key":"2024090911401085000_43.24.4541.31","doi-asserted-by":"crossref","first-page":"7","DOI":"10.1186\/s13024-023-00597-5","article-title":"Anti-malaria drug artesunate prevents development of amyloid-\u03b2 pathology in mice by upregulating PICALM at the blood\u2013brain barrier","volume":"18","author":"Kisler","year":"2023","journal-title":"Mol Neurodegener"},{"key":"2024090911401085000_43.24.4541.32","doi-asserted-by":"crossref","first-page":"429","DOI":"10.1007\/s11357-020-00177-1","article-title":"Single-cell RNA sequencing identifies senescent cerebromicrovascular endothelial cells in the aged mouse brain","volume":"42","author":"Kiss","year":"2020","journal-title":"Geroscience"},{"key":"2024090911401085000_43.24.4541.33","unstructured":"Korotkevich G , Sukhov V , Budin N , Shpak B , Artyomov MN , Sergushichev A (2021) Fast gene set enrichment analysis. bioRxiv 060012."},{"key":"2024090911401085000_43.24.4541.34","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.2008762117"},{"key":"2024090911401085000_43.24.4541.35","doi-asserted-by":"crossref","first-page":"76","DOI":"10.1016\/j.dadm.2017.10.001","article-title":"Lower cerebral blood flow in subjects with Alzheimer's dementia, mild cognitive impairment, and subjective cognitive decline using two-dimensional phase-contrast magnetic resonance imaging","volume":"9","author":"Leijenaar","year":"2017","journal-title":"Alzheimers Dement (Amst)"},{"key":"2024090911401085000_43.24.4541.36","doi-asserted-by":"publisher","DOI":"10.1093\/bioinformatics\/btr260"},{"key":"2024090911401085000_43.24.4541.37","doi-asserted-by":"publisher","DOI":"10.1038\/nprot.2013.092"},{"key":"2024090911401085000_43.24.4541.38","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuron.2014.12.032"},{"key":"2024090911401085000_43.24.4541.39","doi-asserted-by":"publisher","DOI":"10.1007\/s00401-016-1570-0"},{"key":"2024090911401085000_43.24.4541.40","doi-asserted-by":"publisher","DOI":"10.1084\/jem.20171406"},{"key":"2024090911401085000_43.24.4541.41","doi-asserted-by":"publisher","DOI":"10.1038\/ng1180"},{"key":"2024090911401085000_43.24.4541.42","doi-asserted-by":"publisher","DOI":"10.1093\/hmg\/ddaa182"},{"key":"2024090911401085000_43.24.4541.43","doi-asserted-by":"crossref","first-page":"102","DOI":"10.3389\/fnagi.2018.00102","article-title":"Brain transcriptomic analysis of hereditary cerebral hemorrhage with amyloidosis-Dutch type","volume":"10","author":"Moursel","year":"2018","journal-title":"Front Aging Neurosci"},{"key":"2024090911401085000_43.24.4541.44","doi-asserted-by":"publisher","DOI":"10.1038\/s41591-018-0297-y"},{"key":"2024090911401085000_43.24.4541.45","doi-asserted-by":"publisher","DOI":"10.1016\/j.devcel.2013.06.017"},{"key":"2024090911401085000_43.24.4541.46","doi-asserted-by":"publisher","DOI":"10.1001\/archneur.1995.00540310076019"},{"key":"2024090911401085000_43.24.4541.47","unstructured":"Ooms J (2014) The jsonlite package: A practical and consistent mapping between JSON data and R objects. arXiv:1403.2805."},{"key":"2024090911401085000_43.24.4541.48","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCULATIONAHA.119.041433"},{"key":"2024090911401085000_43.24.4541.49","doi-asserted-by":"publisher","DOI":"10.1002\/pmic.200400983"},{"key":"2024090911401085000_43.24.4541.50","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.05-10-02801.1985"},{"key":"2024090911401085000_43.24.4541.51","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuroimage.2017.06.046"},{"key":"2024090911401085000_43.24.4541.52","doi-asserted-by":"publisher","DOI":"10.1101\/cshperspect.a006189"},{"key":"2024090911401085000_43.24.4541.53","doi-asserted-by":"crossref","unstructured":"Serrano-Pozo A , et al . (2022) Astrocyte transcriptomic changes along the spatiotemporal progression of Alzheimer's disease. bioRxiv 518999. https:\/\/doi.org\/10.1101\/2022.12.03.518999.","DOI":"10.21203\/rs.3.rs-2261934\/v1"},{"key":"2024090911401085000_43.24.4541.54","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2019.05.031"},{"key":"2024090911401085000_43.24.4541.55","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0506580102"},{"key":"2024090911401085000_43.24.4541.56","doi-asserted-by":"publisher","DOI":"10.1038\/s41380-019-0609-"},{"key":"2024090911401085000_43.24.4541.57","doi-asserted-by":"crossref","first-page":"1287","DOI":"10.1093\/jnen\/62.12.1287","article-title":"Vascular pathology in Alzheimer disease: correlation of cerebral amyloid angiopathy and arteriosclerosis\/lipohyalinosis with cognitive decline","volume":"62","author":"Thal","year":"2003","journal-title":"J Neuropathol Exp Neurol"},{"key":"2024090911401085000_43.24.4541.58","doi-asserted-by":"publisher","DOI":"10.1038\/nature25739"},{"key":"2024090911401085000_43.24.4541.59","doi-asserted-by":"publisher","DOI":"10.1161\/01.STR.14.6.924"},{"key":"2024090911401085000_43.24.4541.60","doi-asserted-by":"publisher","DOI":"10.1111\/j.1750-3639.1996.tb00799.x"},{"key":"2024090911401085000_43.24.4541.61","first-page":"L1026","article-title":"Induction of stress proteins in human endothelial cells by heavy metal ions and heat shock","volume":"277","author":"Wagner","year":"1999","journal-title":"Am J Physiol"},{"key":"2024090911401085000_43.24.4541.62","doi-asserted-by":"publisher","DOI":"10.1038\/nmeth.2810"},{"key":"2024090911401085000_43.24.4541.63","doi-asserted-by":"publisher","DOI":"10.1038\/s41586-021-04369-3"},{"key":"2024090911401085000_43.24.4541.64","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-020-18249-3"},{"key":"2024090911401085000_43.24.4541.65","doi-asserted-by":"publisher","DOI":"10.1038\/nn.4025"}],"container-title":["The Journal of Neuroscience"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/syndication.highwire.org\/content\/doi\/10.1523\/JNEUROSCI.0237-23.2023","content-type":"unspecified","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/syndication.highwire.org\/content\/doi\/10.1523\/JNEUROSCI.0237-23.2023","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,9,9]],"date-time":"2024-09-09T14:43:33Z","timestamp":1725893013000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.jneurosci.org\/lookup\/doi\/10.1523\/JNEUROSCI.0237-23.2023"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,5,19]]},"references-count":65,"journal-issue":{"issue":"24","published-online":{"date-parts":[[2023,6,14]]},"published-print":{"date-parts":[[2023,6,14]]}},"alternative-id":["10.1523\/JNEUROSCI.0237-23.2023"],"URL":"https:\/\/doi.org\/10.1523\/jneurosci.0237-23.2023","relation":{"has-preprint":[{"id-type":"doi","id":"10.1101\/2023.02.16.528825","asserted-by":"object"}]},"ISSN":["0270-6474","1529-2401"],"issn-type":[{"value":"0270-6474","type":"print"},{"value":"1529-2401","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,5,19]]}}}