期刊
NEUROBIOLOGY OF AGING
卷 37, 期 -, 页码 47-57出版社
ELSEVIER SCIENCE INC
DOI: 10.1016/j.neurobiolaging.2015.10.010
关键词
Alzheimer's Disease Neuroimaging Initiative (ADNI); Alzheimer's disease (AD); Amyloid beta-peptide (A beta); Apolipoprotein E (APOE); Cerebral amyloid angiopathy (CAA); EFAD mice; Karolinska Imaging Dementia Study (KIDS); Microbleeds; Cerebral microbleeds or microhemorrhages; Sex bias
资金
- NIA [R21-AG040683, P01-AG026572, P01AG044682, R21AG030128, R21AG048498, UL1RR029879, P01-AG05142, ADDF]
- National Institute of Biomedical Imaging and Bioengineering
- Alzheimer's Association
- Alzheimer's Drug Discovery Foundation
- Araclon Biotech
- Bio-Clinica, Inc.
- Biogen Idec Inc.
- Bristol-Myers Squibb Company
- Eisai Inc.
- Elan Pharmaceuticals, Inc.
- Eli Lilly
- EuroImmun
- F. Hoffmann-La Roche Ltd.
- Genentech
- Fujirebio
- GE Healthcare
- IXICO Ltd.
- Janssen Alzheimer Immunotherapy Research & Development, LLC.
- Johnson & Johnson Pharmaceutical Research Development
- Medpace, Inc.
- Merck Co., Inc.
- Meso Scale Diagnostics
- NeuroRx Research
- Neurotrack Technologies
- Novartis Pharmaceuticals
- Pfizer Inc.
- Piramal Imaging
- Servier
- Synarc
- Takeda Pharmaceutical Company
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 Ab also showed female excess. Both the cerebral microbleeds and cerebral amyloid angiopathy increased in proportion to individual Ab 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. (C) 2016 Elsevier Inc. All rights reserved.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据