Sex Differences in Amyloid Pathology by Race, Ancestry, and Apolipoprotein E ε4 in an Admixed Autopsy Sample

Do male and female individuals differ in neuritic plaque deposition, and does sex modify the influence of apolipoprotein E ε4, informant-reported race, or African genetic ancestry on plaque burden?In this cross-sectional study of 2268 autopsied adults, female sex was independently associated with greater neuritic plaque burden, especially White female individuals; among participants with moderate/frequent plaques, female individuals were more likely to reach high tau stages than male individuals, but sex did not modify the effect. The association between and neuritic plaque burden varied by race and African ancestry, with lower plaque burden observed in Black individuals and those with African ancestry only among ε4 noncarriers; among ε4 carriers, plaque burden did not differ by race or ancestry.In this study, amyloid and tau burdens were higher in women, and ancestry modulated -related risk, underscoring the need for sex- and ancestry-specific thresholds in Alzheimer disease risk assessment and targeted interventions.

Corresponding Author: Lea T. Grinberg, MD, PhD, Laboratory Medicine and Pathology Department, Mayo Clinic, 4500 San Pablo Rd, Jacksonville, FL 32257 (grinberg.lea@mayo.edu).

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