Increased APOE ε4 expression is associated with the difference in Alzheimer's disease risk from diverse ancestral backgrounds

• DOI: 10.1002/alz.12287
• Publication Date: 2021-02-01T08:40:14Z
• Authors: Anthony J. Griswold; Katrina Celis; Parker L. Bussies; Farid Rajabli; Patrice L. Whitehead; Kara L. Hamilton‐...; Gary W. Beecham; Derek M. Dykxhoorn; Karen Nuytemans; Liyong Wang; Olivia K. Gardner; Daniel A. Dorfsman; Eileen H. Bigio; Marek Marsel Mesulam; Sandra Weintraub; Changiz Geula; Marla Gearing; Elisa McGrath‐Mar...; Clifton L. Dalgard; William K. Scott; Jonathan L. Haines; Margaret A. Peric...; Juan I. Young; Jeffery M. Vance
• Keywords: Apolipoprotein E

Abstract Introduction Apolipoprotein E ( APOE ) ε4 confers less risk for Alzheimer's disease (AD) in carriers with African local genomic ancestry (ALA) than European (ELA). Cell type specific transcriptional variation between the two ancestries (LAs) could contribute to this differences. Methods Single‐nucleus RNA sequencing was performed on frozen frontal cortex of homozygous ε4/ε4 AD patients: seven ELA, four ALA. Results A total 60,908 nuclei were sequenced. Within LA region (chr19:44‐46Mb), gene most differentially expressed, ELA having significantly more expression (overall P < 1.8E –317 24 32 cell clusters. The transcriptome one astrocyte cluster, high and is suggestive A1 reactive astrocytes. Discussion patients expressed greater levels ALA carriers. These differences reduced seen