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Endothelial Cells Are Heterogeneous in Different Brain Regions and Are Dramatically Altered in Alzheimer's Disease.
Bryant, Annie; Li, Zhaozhi; Jayakumar, Rojashree; Serrano-Pozo, Alberto; Woost, Benjamin; Hu, Miwei; Woodbury, Maya E; Wachter, Astrid; Lin, Gen; Kwon, Taekyung; Talanian, Robert V; Biber, Knut; Karran, Eric H; Hyman, Bradley T; Das, Sudeshna; Bennett, Rachel E.
Afiliação
  • Bryant A; Department of Neurology, Harvard Medical School, MassGeneral Institute for Neurodegenerative Disease, Massachusetts General Hospital, Charlestown, Massachusetts 02129.
  • Li Z; Department of Neurology, Harvard Medical School, MassGeneral Institute for Neurodegenerative Disease, Massachusetts General Hospital, Charlestown, Massachusetts 02129.
  • Jayakumar R; Department of Neurology, Harvard Medical School, MassGeneral Institute for Neurodegenerative Disease, Massachusetts General Hospital, Charlestown, Massachusetts 02129.
  • Serrano-Pozo A; Department of Neurology, Harvard Medical School, MassGeneral Institute for Neurodegenerative Disease, Massachusetts General Hospital, Charlestown, Massachusetts 02129.
  • Woost B; Department of Neurology, Harvard Medical School, MassGeneral Institute for Neurodegenerative Disease, Massachusetts General Hospital, Charlestown, Massachusetts 02129.
  • Hu M; Department of Neurology, Harvard Medical School, MassGeneral Institute for Neurodegenerative Disease, Massachusetts General Hospital, Charlestown, Massachusetts 02129.
  • Woodbury ME; AbbVie, Cambridge Research Center, Cambridge, Massachusetts 02139.
  • Wachter A; AbbVie Deutschland GmbH & Company KG, Genomics Research Center, Ludwigshafen, 67061, Germany.
  • Lin G; AbbVie Deutschland GmbH & Company KG, Genomics Research Center, Ludwigshafen, 67061, Germany.
  • Kwon T; AbbVie, Cambridge Research Center, Cambridge, Massachusetts 02139.
  • Talanian RV; AbbVie, Cambridge Research Center, Cambridge, Massachusetts 02139.
  • Biber K; AbbVie Deutschland GmbH & Company KG, Genomics Research Center, Ludwigshafen, 67061, Germany.
  • Karran EH; AbbVie, Cambridge Research Center, Cambridge, Massachusetts 02139.
  • Hyman BT; Department of Neurology, Harvard Medical School, MassGeneral Institute for Neurodegenerative Disease, Massachusetts General Hospital, Charlestown, Massachusetts 02129.
  • Das S; Department of Neurology, Harvard Medical School, MassGeneral Institute for Neurodegenerative Disease, Massachusetts General Hospital, Charlestown, Massachusetts 02129.
  • Bennett RE; Department of Neurology, Harvard Medical School, MassGeneral Institute for Neurodegenerative Disease, Massachusetts General Hospital, Charlestown, Massachusetts 02129 rebennett@mgh.harvard.edu.
J Neurosci ; 43(24): 4541-4557, 2023 06 14.
Article em En | MEDLINE | ID: mdl-37208174
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 ß 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.SIGNIFICANCE STATEMENT 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.
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Texto completo: 1 Base de dados: MEDLINE Assunto principal: Angiopatia Amiloide Cerebral / Doença de Alzheimer Limite: Aged / Female / Humans / Male Idioma: En Ano de publicação: 2023 Tipo de documento: Article

Texto completo: 1 Base de dados: MEDLINE Assunto principal: Angiopatia Amiloide Cerebral / Doença de Alzheimer Limite: Aged / Female / Humans / Male Idioma: En Ano de publicação: 2023 Tipo de documento: Article