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


CONCLUSIONS
Our data provide support for TOMM40 variant repeat length as an important contributor to AD-like MTL pathology in the absence of APOE ε4.
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.
Alison C
AC
Burggren
Department of Psychiatry and Biobehavioral Sciences, University of California, Los Angeles, CA, USA.
Zanjbeel
Z
Mahmood
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.
Theresa M
TM
Harrison
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.
Prabha
P
Siddarth
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.
Karen J
KJ
Miller
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.
Gary W
GW
Small
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.
David A
DA
Merrill
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.
Susan Y
SY
Bookheimer
D000368:Aged; D000544:Alzheimer Disease / Q000235:genetics; D053327:Apolipoprotein E4 / Q000235:genetics*; D018728:Entorhinal Cortex / Q000473:pathology; D005260:Female; D005838:Genotype; D064368:Healthy Volunteers; D006624:Hippocampus / Q000473:pathology*; D006801:Humans; D015810:Linkage Disequilibrium; D008279:Magnetic Resonance Imaging; D008297:Male; D026901:Membrane Transport Proteins / Q000235:genetics*; D008875:Middle Aged; D000090622:Mitochondrial Precursor Protein Import Complex Proteins; D013702:Temporal Lobe / Q000473:pathology
D053327:Apolipoprotein E4; D026901:Membrane Transport Proteins; D000090622:Mitochondrial Precursor Protein Import Complex Proteins; C400783:TOMM40 protein, human
APOE; Alzheimer's disease; Entorhinal cortex; Hippocampus; MRI; TOMM40