Apolipoprotein epsilon 4 Is Associated with Lower Brain Volume in Cognitively Normal Chinese but Not White Older Adults

Abstract

Studying ethnically diverse groups is important for furthering our understanding of biological mechanisms of disease that may vary across human populations. The epsilon 4 allele of apolipoprotein E (APOE epsilon 4) 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 epsilon 4 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 epsilon 4 plays in moderating brain volume in cognitively normal Chinese older adults, compared to older white Americans. We hypothesized that carrying APOE epsilon 4 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 epsilon 4 and being Chinese. The APOE epsilon 4xChinese interaction was associated with lower volume in bilateral cuneus and left middle frontal gyrus (P-uncorrected<0.001), with suggestive findings in right entorhinal cortex and left hippocampus (P-uncorrected<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 (P-FWE = 0.05). Our study suggests there is a differential effect of APOE epsilon 4 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 epsilon 4 effects on the brain in diverse populations.