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Hippocampal thinning linked to longer TOMM40 poly‐T variant lengths in the absence of the APOE ε4 variant
Author(s) -
Burggren Alison C.,
Mahmood Zanjbeel,
Harrison Theresa M.,
Siddarth Prabha,
Miller Karen J.,
Small Gary W.,
Merrill David A.,
Bookheimer Susan Y.
Publication year - 2017
Publication title -
alzheimer's and dementia
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 6.713
H-Index - 118
eISSN - 1552-5279
pISSN - 1552-5260
DOI - 10.1016/j.jalz.2016.12.009
Subject(s) - apolipoprotein e , entorhinal cortex , hippocampal formation , biology , allele , neurotoxicity , neuroscience , genetics , medicine , disease , gene , toxicity
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 ε4 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 ε4 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 ε4.