Apolipoprotein ε4 is associated with lower brain volume in cognitively normal Chinese but not white older adults.
Studying ethnically diverse groups is important for furthering our understanding of biological mechanisms of disease that may vary across human populations. The ε4 allele of apolipoprotein E (APOE ε4) is a well-established risk factor for Alzheimer's disease (AD), and may confer anatomic and functional effects years before clinical signs of cognitive decline are observed. The allele frequency of APOE ε4 varies both across and within populations, and the size of the effect it confers for dementia risk may be affected by other factors. Our objective was to investigate the role APOE ε4 plays in moderating brain volume in cognitively normal Chinese older adults, compared to older white Americans. We hypothesized that carrying APOE ε4 would be associated with reduced brain volume and that the magnitude of this effect would be different between ethnic groups. We performed whole brain analysis of structural MRIs from Chinese living in America (n = 41) and Shanghai (n = 30) and compared them to white Americans (n = 71). We found a significant interaction effect of carrying APOE ε4 and being Chinese. The APOE ε4xChinese interaction was associated with lower volume in bilateral cuneus and left middle frontal gyrus (Puncorrected<0.001), with suggestive findings in right entorhinal cortex and left hippocampus (Puncorrected<0.01), all regions that are associated with neurodegeneration in AD. After correction for multiple testing, the left cuneus remained significantly associated with the interaction effect (PFWE = 0.05). Our study suggests there is a differential effect of APOE ε4 on brain volume in Chinese versus white cognitively normal elderly adults. This represents a novel finding that, if verified in larger studies, has implications for how biological, environmental and/or lifestyle factors may modify APOE ε4 effects on the brain in diverse populations.
Department of Neurology, University of California San Francisco, San Francisco, California, United States of America.
Jennifer S
JS
Yokoyama
Department of Neurology, University of California San Francisco, San Francisco, California, United States of America.
Allen K L
AK
Lee
Department of Neurology, University of California San Francisco, San Francisco, California, United States of America; Hospital das Clinicas, University of Sao Paulo Medical School, Sao Paulo, Brazil.
Leonel T
LT
Takada
Department of Neurology, University of California San Francisco, San Francisco, California, United States of America.
Edgar
E
Busovaca
Department of Neurology, University of California San Francisco, San Francisco, California, United States of America.
Luke W
LW
Bonham
Department of Neurology, Veterans Affairs Health Care system, Palo Alto, California, United States of America; Department of Neurology and Neurological Science, Stanford University School of Medicine, Stanford, California, United States of America.
Steven Z
SZ
Chao
Department of Neurology, University of California San Francisco, San Francisco, California, United States of America.
Marian
M
Tse
Department of Neurology, University of California Davis, Davis, California, United States of America.
Jing
J
He
Department of Radiology, Mayo Clinic and Foundation, Rochester, Minnesota, United States of America.
Christopher G
CG
Schwarz
Department of Neurology, University of California Davis, Davis, California, United States of America; Department of Computer Science, University of California Davis, Davis, California, United States of America.
Owen T
OT
Carmichael
Department of Neurology, Indiana University School of Medicine, Indianapolis, Indiana, United States of America.
Brandy R
BR
Matthews
Department of Neurology, University of California San Francisco, San Francisco, California, United States of America.
Anna
A
Karydas
Department of Veterans Affairs Medical Center, Center for Imaging of Neurodegenerative Diseases, San Francisco, California, United States of America; Department of Radiology, University of California San Francisco, California, United States of America.
Michael W
MW
Weiner
Departments of Psychiatry & Neurology, Semel Institute for Neuroscience and Human Behavior, University of California Los Angeles, Los Angeles, California, United States of America.
Giovanni
G
Coppola
Department of Neurology, University of California Davis, Davis, California, United States of America.
Charles S
CS
DeCarli
Department of Neurology, University of California San Francisco, San Francisco, California, United States of America.
Bruce L
BL
Miller
Department of Neurology, University of California San Francisco, San Francisco, California, United States of America.
Howard J
HJ
Rosen
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000375:Aging / Q000208:ethnology / Q000235:genetics* / Q000502:physiology; D000483:Alleles; D053327:Apolipoprotein E4 / Q000235:genetics*; D001921:Brain / Q000254:growth & development / Q000378:metabolism / Q000502:physiology*; D002681:China; D003071:Cognition; D005260:Female; D006801:Humans; D008279:Magnetic Resonance Imaging; D008297:Male; D008875:Middle Aged; D009929:Organ Size
D053327:Apolipoprotein E4