Associations between haplotypes and limbic system white matter microstructure.

INTRODUCTION

We assessed associations between apolipoprotein E Translocase of Outer Mitochondrial Membrane 40 (-'523 haplotypes and white matter microstructure (WMM) across limbic tracts important for memory and cognition in non-Hispanic Black and White individuals.

METHODS

Linear regression models, stratified by and racialized groups, assessed associations between -'523-S and limbic tract WMM free-water (FW) and free-water-corrected fractional anisotropy (FAFWcorr).

RESULTS

Black-ε4+-one-'523-S carriers had lower FW in the cingulum and inferior longitudinal fasciculus compared to Black-ε4+-no-'523-S carriers. Additionally, Black-ε4+-one-'523-S carriers had lower FW in the cingulum, uncinate, and fornix, and higher FA in the uncinate compared to Black-ε4+-'523-S/S carriers. White-ε3/ε3-'523-S/S carriers had lower FAFWcorr in the cingulum and inferior temporal gyrus compared to White-ε3/ε3-no-'523-S carriers, and lower FAFWcorr in the cingulum compared to White-ε3/ε3-one-'523-S carriers.

DISCUSSION

This supports prior work that '523-S is associated with abnormal aging in White-ε3/ε3 carriers, but is potentially risk-mitigating in Black-ε4+ carriers, while suggesting a differential effect by racialized background of on WMM.

HIGHLIGHTS

White matter microstructure (WMM) across limbic tracts important for cognition was measured by diffusion MRI.Black apolipoprotein E (APOE) ε4+ carriers with one copy of TOMM40-'523-S had normal aging WMM metrics across several tracts, including the cingulum bundle, uncinate fasciculus, fornix, and inferior longitudinal fasciculus.White APOE ε3/ε3 carriers with two copies of TOMM40-'523-S had abnormal aging WMM metrics in the cingulum bundle and inferior temporal gyrus.APOE associations with aging may differ in racialized groups due to TOMM40-'523-S copy number.