TOMM40 may mediate GFAP, neurofilament light Protein, pTau181, and brain morphometry in aging.

A growing amount of data has implicated the gene in the risk for Alzheimer's disease (AD), neurodegeneration, and accelerated aging. No studies have investigated the relationship of rs2075650 ('650 on the structural complexity of the brain or plasma markers of neurodegeneration. We used a comprehensive approach to quantify the impact of '650 on brain morphology and multiple cortical attributes in cognitively unimpaired (CU) individuals. We also tested whether the presence of the risk allele, G, of '650 was associated with plasma markers of amyloid, tau, and neurodegeneration and if there were interactions with age and sex, controlling for the effects of ε4. We found that the '650 G-allele was associated with decreased sulcal depth, increased gyrification index, and decreased gray matter volume. NfL, GFAP, and pTau181 had independent and age-associated increases in individuals with a G-allele. Our data suggest that '650 is associated with aging-related plasma biomarkers and brain structure variation in temporal-limbic circuits.