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

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