The APOE4 allele shows opposite sex bias in microbleeds and Alzheimer's disease of humans and mice.

Journal Article (Journal Article)

The apolipoprotein APOE4 allele confers greater risk of Alzheimer's disease (AD) for women than men, in conjunction with greater clinical deficits per unit of AD neuropathology (plaques, tangles). Cerebral microbleeds, which contribute to cognitive dysfunctions during AD, also show APOE4 excess, but sex-APOE allele interactions are not described. We report that elderly men diagnosed for mild cognitive impairment and AD showed a higher risk of cerebral cortex microbleeds with APOE4 allele dose effect in 2 clinical cohorts (ADNI and KIDS). Sex-APOE interactions were further analyzed in EFAD mice carrying human APOE alleles and familial AD genes (5XFAD (+/-) /human APOE(+/+)). At 7 months, E4FAD mice had cerebral cortex microbleeds with female excess, in contrast to humans. Cerebral amyloid angiopathy, plaques, and soluble Aβ also showed female excess. Both the cerebral microbleeds and cerebral amyloid angiopathy increased in proportion to individual Aβ load. In humans, the opposite sex bias of APOE4 allele for microbleeds versus the plaques and tangles is the first example of organ-specific, sex-linked APOE allele effects, and further shows AD as a uniquely human condition.

Full Text

Duke Authors

Cited Authors

  • Cacciottolo, M; Christensen, A; Moser, A; Liu, J; Pike, CJ; Smith, C; LaDu, MJ; Sullivan, PM; Morgan, TE; Dolzhenko, E; Charidimou, A; Wahlund, L-O; Wiberg, MK; Shams, S; Chiang, GC-Y; Alzheimer's Disease Neuroimaging Initiative, ; Finch, CE

Published Date

  • January 2016

Published In

Volume / Issue

  • 37 /

Start / End Page

  • 47 - 57

PubMed ID

  • 26686669

Pubmed Central ID

  • PMC4687024

Electronic International Standard Serial Number (EISSN)

  • 1558-1497

Digital Object Identifier (DOI)

  • 10.1016/j.neurobiolaging.2015.10.010


  • eng

Conference Location

  • United States