Increased APOEϵ4 expression is associated with reactive A1 astrocytes and the difference in Alzheimer Disease risk from diverse ancestral backgrounds

Katrina Celis; Anthony J. Griswold; Parker L. Bussies; Farid Rajabli; Patrice L. Whitehead; Kara L. Hamilton‐Nelson; Gary W. Beecham; Derek Michael Dykxhoorn; Karen Nuytemans; Liyong Wang; Olivia K. Gardner; Daniel A. Dorfsman; Eileen H. Bigio; Marsel M. Mesulam; Sandra Weıntraub; Changiz Geula; Marla Gearing; Clifton L. Dalgard; Elisa McGrath Martinez; William K. Scott; Jonathan L. Haines; Margaret Ann Pericak‐Vance; Juan I. Young; Jeffery M. Vance

doi:10.1002/alz.045415

GenomicsAlzheimer s & DementiaDec 1, 2020

Peer-reviewed journal article

Increased APOEϵ4 expression is associated with reactive A1 astrocytes and the difference in Alzheimer Disease risk from diverse ancestral backgrounds

Katrina Celis, Anthony J. Griswold iD, Parker L. Bussies iD, Farid Rajabli iD, Patrice L. Whitehead, Kara L. Hamilton‐Nelson iD, Gary W. Beecham iD, Derek Michael Dykxhoorn iD, Karen Nuytemans iD, Liyong Wang iD, Olivia K. Gardner iD, Daniel A. Dorfsman, Eileen H. Bigio iD, Marsel M. Mesulam iD, Sandra Weıntraub iD, Changiz Geula iD, Marla Gearing iD, Clifton L. Dalgard iD, Elisa McGrath Martinez, William K. Scott iD, Jonathan L. Haines iD, Margaret Ann Pericak‐Vance iD, Juan I. Young iD, Jeffery M. Vance iD

Abstract

APOE{varepsilon}4 African local genomic ancestry (LA) confers less risk for Alzheimer disease (AD) relative to European LA (LA) carriers. Single nucleus RNA sequencing from AD-APOE{varepsilon}4/4 frontal cortex found European LA carriers have a 1.45-fold greater APOE{varepsilon}4 expression (p< 1.8 E10-313) and are associated with a unique A1 reactive astrocyte cluster. This suggests a potential mechanism for the increased risk for AD seen in European LA carriers of APOE{varepsilon}4.

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