Apolipoprotein E and Alzheimer disease: risk, mechanisms and therapy

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	Apolipoprotein E and Alzheimer disease: risk, mechanisms and therapy
	Liu, Chia-Chan ; Kanekiyo, Takahisa ; Xu, Huaxi ; Bu, Guojun ; Xu HX(许华曦) ; Bu GJ(卜国军)
刊名	http://dx.doi.org/10.1038/nrneurol.2012.263
	2013
关键词	MILD COGNITIVE IMPAIRMENT CEREBRAL AMYLOID ANGIOPATHY CENTRAL-NERVOUS-SYSTEM APOE EPSILON-4 ALLELE DENSITY-LIPOPROTEIN RECEPTOR GENOME-WIDE ASSOCIATION BETA-PEPTIDE DEPOSITION E TYPE-4 ALLELE E GENOTYPE A-BETA
英文摘要	NIH; Alzheimer's Association; American Health Assistance Foundation; Xiamen University Research Funds; Apolipoprotein E (Apo-E) is a major cholesterol carrier that supports lipid transport and injury repair in the brain. APOE polymorphic alleles are the main genetic determinants of Alzheimer disease (AD) risk: individuals carrying the epsilon 4 allele are at increased risk of AD compared with those carrying the more common epsilon 3 allele, whereas the epsilon 2 allele decreases risk. Presence of the APOE epsilon 4 allele is also associated with increased risk of cerebral amyloid angiopathy and age-related cognitive decline during normal ageing. Apo-E-lipoproteins bind to several cell-surface receptors to deliver lipids, and also to hydrophobic amyloid-beta (A beta) peptide, which is thought to initiate toxic events that lead to synaptic dysfunction and neurodegeneration in AD. Apo-E isoforms differentially regulate A beta aggregation and clearance in the brain, and have distinct functions in regulating brain lipid transport, glucose metabolism, neuronal signalling, neuroinflammation, and mitochondrial function. In this Review, we describe current knowledge on Apo-E in the CNS, with a particular emphasis on the clinical and pathological features associated with carriers of different Apo-E isoforms. We also discuss A beta-dependent and A beta-independent mechanisms that link Apo-E4 status with AD risk, and consider how to design effective strategies for AD therapy by targeting Apo-E. Liu, C.-C. et al. Nat. Rev. Neurol. 9, 106-118 (2013); published online 8 January 2013; doi:10.1038/nrneurol.2012.263
语种	英语
出版者	NATURE PUBLISHING GROUP
内容类型	期刊论文
源URL	[http://dspace.xmu.edu.cn/handle/2288/93398]
专题	医学院－已发表论文
推荐引用方式 GB/T 7714	Liu, Chia-Chan,Kanekiyo, Takahisa,Xu, Huaxi,et al. Apolipoprotein E and Alzheimer disease: risk, mechanisms and therapy[J]. http://dx.doi.org/10.1038/nrneurol.2012.263,2013.
APA	Liu, Chia-Chan,Kanekiyo, Takahisa,Xu, Huaxi,Bu, Guojun,许华曦,&卜国军.(2013).Apolipoprotein E and Alzheimer disease: risk, mechanisms and therapy.http://dx.doi.org/10.1038/nrneurol.2012.263.
MLA	Liu, Chia-Chan,et al."Apolipoprotein E and Alzheimer disease: risk, mechanisms and therapy".http://dx.doi.org/10.1038/nrneurol.2012.263 (2013).