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

A growing amount of data has implicated the TOMM40 gene in the risk for Alzheimer's disease (AD), neurodegeneration, and accelerated aging. No studies have investigated the relationship of TOMM40 rs2075650 ('650) on the structural complexity of the brain or plasma markers of neurodegeneration. We used a comprehensive approach to quantify the impact of TOMM40 '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 TOMM40 '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 APOE ε4. We found that the TOMM40 '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 TOMM40 '650 is associated with aging-related plasma biomarkers and brain structure variation in temporal-limbic circuits.