Apolipoprotein ε4 Is Associated with Lower Brain Volume in Cognitively Normal Chinese but Not White Older Adults
Year: 2015
Type: article
Study design: Observational Study
Abstract: 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.
Source: PLoS ONE
Authors: Jennifer S. Yokoyama, Allen K. L. Lee, Leonel T. Takada, Edgar Busovaca, Luke W. Bonham, Steven Z. Chao, Marian Tse, Jing He, Christopher G. Schwarz, Owen T. Carmichael, Brandy R. Matthews, Anna Karydas, Michael W. Weiner, Giovanni Coppola, Charles S. DeCarli, Bruce L. Miller, Howard J. Rosen
Institutions: University of California, San Francisco, Universidade de São Paulo, Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo, United States Department of Veterans Affairs, VA Palo Alto Health Care System, Stanford Medicine, Stanford University, University of California, Davis, Mayo Clinic, Indiana University School of Medicine, San Francisco VA Medical Center, University of California, Los Angeles
Language: English
Subfield: Psychiatry and Mental health
Field: Medicine
Domain: Health Sciences
Open Access status: gold
Estimated APC paid: $2,382
Awards: G104586243, G1264619266, G1264679647, UC Davis Alzheimer's Disease Core Center, Genetic, Genomic, and Imaging Biomarkers in Degenerative Dementia, G1888650583, Indiana Clinical and Translational Sciences Institute, G2735560116, G2957681590, G3146424788, G3182212420, RNA signatures of frontotemporal dementia and ALS due to C9ORF72 expansion, G4894255983, G5004681328, G535778942, G544417212, G570682065, Alzheimer's Disease Neuroimaging Initiative, G603598372, G6174240121, G6492025387, G6790119021, G7985004527, G801680829, Multimodal Imaging in Frontotemporal Degeneration, G9000018678, G9000036492, G9000095007, G9000122335, G9000162592, G9000234615, Frontotemporal Dementia: Genes, Images, and Emotions, Alzheimer's Disease Neuroimaging Initiative (ADNI4)
OpenAlex ID: W2029601850