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

Publication Type	Academic Article
Authors	Cacciottolo M, Christensen A, Moser A, Liu J, Pike C, Smith C, LaDu M, Sullivan P, Morgan T, Dolzhenko E, Charidimou A, Wahlund L, Wiberg M, Shams S, Chiang G, Finch C
Journal	Neurobiol Aging
Volume	37
Pagination	47-57
Date Published	10/19/2015
ISSN	1558-1497
Keywords	Alleles, Alzheimer Disease, Apolipoproteins E, Cerebral Hemorrhage, Genetic Association Studies, Sex Characteristics
Abstract	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.
DOI	10.1016/j.neurobiolaging.2015.10.010
PubMed ID	26686669
PubMed Central ID	PMC4687024