APOE ε4 and resting-state functional connectivity in racially/ethnically diverse older adults

Numerous neuroimaging studies demonstrated an association between the apolipoprotein E (APOE) ε4 allele and resting-state functional connectivity (rsFC) of regions within the default mode network (DMN), both in healthy populations and patients with AD. It remains unclear whether the APOE ε4 allele differentially affects the brain's functional network architecture across race/ethnicity.

We investigated rsFC within DMN subsystems in 170 APOE ε4 carriers compared to 387 APOE ε4 non-carriers across three major racial/ethnic groups, including non-Hispanic Whites (n = 166), non-Hispanic Blacks (n = 185), and Hispanics (n = 206) from the Washington Heights-Inwood Columbia Aging Project.

Compared to APOE ε4 non-carriers, APOE ε4 carriers had lower rsFC in temporal DMN, but only in non-Hispanic Whites. Non-Hispanic Black and Hispanic APOE ε4 carriers had slightly higher or similar rsFC compared with non-Hispanic White APOE ε4 non-carriers.

These findings suggest that APOE ε4 modulates DMN rsFC differently in non-Hispanic Whites compared with non-Hispanic Blacks and Hispanics.