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

bioRxiv, March 2020

A. J. Griswold, K. Celis, P. Bussies, F. Rajabli, P. Whitehead, K. Hamilton-Nelson, G. W. Beecham, D. M. Dykxhoorn, K. Nuytemans, L. Wang, O. K. Gardner, D. Dorfsman, E.H. Bigio, M. Mesulam, S. Weintraub, C. Geula, M. Gearing, E. Martinez-McGrath, C.L. Dalgard, W. K. Scott, J. L. Haines, M.A. Pericak-Vance, J. I. Young, J. M. Vance

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.