Hippocampal thinning linked to longer TOMM40 poly-T variant lengths in the absence of the APOE ε4 variant.

Introduction: The translocase of outer mitochondrial membrane 40 (TOMM40), which lies in linkage disequilibrium with apolipoprotein E (APOE), has received attention more recently as a promising gene in Alzheimer's disease (AD) risk. TOMM40 influences AD pathology through mitochondrial neurotoxicity, and the medial temporal lobe (MTL) is the most likely brain region for identifying early manifestations of AD-related morphology changes. Methods: In this study, we examined the effects of TOMM40 using high-resolution magnetic resonance imaging in 65 healthy, older subjects with and without the APOE epsilon 4 AD-risk variant. Results: Examining individual subregions within the MTL, we found a significant relationship between increasing poly-T lengths of the TOMM40 variant and thickness of the entorhinal cortex only in subjects who did not carry the APOE epsilon 4 allele. Discussion: Our data provide support for TOMM40 variant repeat length as an important contributor to AD-like MTL pathology in the absence of APOE epsilon 4. Published by Elsevier Inc. on behalf of the Alzheimer's Association.