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

Journal Article · Tue Feb 07 00:00:00 EST 2017 · Alzheimer's & Dementia

DOI:https://doi.org/10.1016/j.jalz.2016.12.009· OSTI ID:1550604

Burggren, Alison C. ^[1]; Mahmood, Zanjbeel ^[2]; Harrison, Theresa M. ^[3]; Siddarth, Prabha ^[4]; Miller, Karen J. ^[4]; Small, Gary W. ^[4]; Merrill, David A. ^[4]; Bookheimer, Susan Y. ^[5]

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1. Center for Cognitive Neurosciences University of California Los Angeles CA USA, Department of Psychiatry and Biobehavioral Sciences University of California Los Angeles CA USA, Semel Institute for Neuroscience and Human Behavior, David Geffen School of Medicine University of California Los Angeles CA USA
2. Department of Psychiatry and Biobehavioral Sciences University of California Los Angeles CA USA
3. Center for Cognitive Neurosciences University of California Los Angeles CA USA, Department of Psychiatry and Biobehavioral Sciences University of California Los Angeles CA USA, Interdepartmental Graduate Program in Neuroscience University of California Los Angeles CA USA
4. Department of Psychiatry and Biobehavioral Sciences University of California Los Angeles CA USA, Semel Institute for Neuroscience and Human Behavior, David Geffen School of Medicine University of California Los Angeles CA USA, Division of Geriatric Psychiatry, Longevity Center University of California Los Angeles CA USA
5. Center for Cognitive Neurosciences University of California Los Angeles CA USA, Department of Psychiatry and Biobehavioral Sciences University of California Los Angeles CA USA, Semel Institute for Neuroscience and Human Behavior, David Geffen School of Medicine University of California Los Angeles CA USA, Department of Psychology University of California Los Angeles CA USA

Abstract 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 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.

• Sponsoring Organization: USDOE
• Grant/Contract Number: DE‐FC03‐87‐ER60615
• OSTI ID: 1550604
• Journal Information: Alzheimer's & Dementia, Journal Name: Alzheimer's & Dementia Vol. 13 Journal Issue: 7; ISSN 1552-5260
• Publisher: Wiley Blackwell (John Wiley & Sons)
• Country of Publication: United States
• Language: English