Alison C Burggren1, Zanjbeel Mahmood2, Theresa M Harrison3, Prabha Siddarth4, Karen J Miller4, Gary W Small4, David A Merrill4, Susan Y Bookheimer5. 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. Electronic address: aclement@ucla.edu. 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. Published by Elsevier Inc.
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. Published by Elsevier Inc.
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