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.

Proteome profiling of cerebrospinal fluid using machine learning shows a unique protein signature associated with APOE4 genotype.

Proteome changes associated with APOE4 variant carriage that are independent of Alzheimer's disease (AD) pathology and diagnosis are unknown. This study investigated APOE4 proteome changes in people with AD, mild cognitive impairment, and no impairment. Clinical, APOE genotype, and cerebrospinal fluid (CSF) proteome and AD biomarker data was sourced from the Alzheimer's Disease Neuroimaging Initiative (ADNI) database.

Association of APOE alleles and polygenic profiles comprising APOE-TOMM40-APOC1 variants with Alzheimer's disease neuroimaging markers.

Introduction: TOMM40 and APOC1 variants can modulate the APOE-ε4-related Alzheimer's disease (AD) risk by up to fourfold. We aim to investigate whether the genetic modulation of ε4-related AD risk is reflected in brain morphology.

Methods: We tested whether 27 magnetic resonance imaging-derived neuroimaging markers of neurodegeneration (volume and thickness in temporo-limbic regions) are associated with APOE-TOMM40-APOC1 polygenic profiles using the National Alzheimer's Coordinating Center Uniform Data Set linked to the AD Genetic Consortium data.