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

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

doi:10.1101/2020.03.09.983817

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bioRxiv · 10.1101/2020.03.09.983817

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

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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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Griswold, A. J., Celis, K., Bussies, P., Rajabli, F., Whitehead, P., Hamilton-Nelson, K., Beecham, G. W., Dykxhoorn, D. M., Nuytemans, K., Wang, L., Gardner, O. K., Dorfsman, D., Bigio, E. H., Mesulam, M.-M., Weintraub, S., Geula, C., Gearing, M., Martinez-McGrath, E., Dalgard, C. L., Scott, W. K., Haines, J. L., Pericak-Vance, M. A., Young, J. I., Vance, J. M.. 2020-03-11. Increased APOEϵ4 expression is associated with reactive A1 astrocytes and the difference in Alzheimer Disease risk from diverse ancestral backgrounds. https://doi.org/10.1101/2020.03.09.983817

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