DOI: 10.1002/alz.075762 ISSN: 1552-5260

Brain structural changes associated with Apoe2 in 3041 subjects from the UK Biobank

Priya Rajagopalan
  • Psychiatry and Mental health
  • Cellular and Molecular Neuroscience
  • Geriatrics and Gerontology
  • Neurology (clinical)
  • Developmental Neuroscience
  • Health Policy
  • Epidemiology

Abstract

Background

Common variants in the apolipoprotein E gene are the greatest known source of genetic risk for late‐onset Alzheimer’s disease (AD). Carriers of one or more copies of the ε4 allele are more likely to develop AD, but carriers of the ε2 allele have a lower incidence of AD (1,2,3). Mechanisms underlying this effect are not fully understood, motivating comparisons of brain imaging data in people carrying different APOE genotypes. Prior voxel‐based morphometry (VBM) studies have reported gray matter alterations in medial temporal and precuneal regions in people with AD (4) and in healthy APOE ε4 carriers (5) but less is known about the effect of APOE ε2 compared to ε4 carrier status on gray matter volume in elderly adults.

Method

The ENIGMA voxel based morphometry (VBM; https://sites.google.com/view/enigmavbm; 6) pipeline was used to perform a large‐scale analysis of 3D T1‐weighted brain MRI data from 3,041 older adult participants (45.5% female; 72.0 (6.2SD) years old) from the UK Biobank (UKBB). Subject demographics are outlined in Table 1. The statistical relationship between voxel‐wise brain gray and white matter volumes and APOE2 genotype was assessed using linear mixed models, adjusting for age, sex, intracranial volume, population structure, and scan site. All associations were corrected for multiple comparisons using the standard false discovery rate method.

Result

Significantly larger volumes were detected in subcortical gray and deep white matter regions of the brain for the APOE ε2 genotype, while smaller volumes were noted in the peripheral cortex and juxtacortical white matter, when controlling for FDR at q = 0.05 (gray matter critical P‐value 0.008 and white matter critical P‐value 0.01). Significance values and brain maps for the APOE ε2 genotype are outlined in Figure 1 and Figure 2.

Conclusion

We identified alterations in gray and white matter volumes related to presence of at least one APOE2 allele. These results support prior reports that elderly adult carriers of the APOE2 haplotype have, on average, neurostructural alterations in gray matter architecture, even after adjusting for the effects of ancestry and age.

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