Document Detail


Apolipoprotein E and Alzheimer disease: risk, mechanisms and therapy.
MedLine Citation:
PMID:  23296339     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
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 ε4 allele are at increased risk of AD compared with those carrying the more common ε3 allele, whereas the ε2 allele decreases risk. Presence of the APOE ε4 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-β (Aβ) peptide, which is thought to initiate toxic events that lead to synaptic dysfunction and neurodegeneration in AD. Apo-E isoforms differentially regulate Aβ 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 Aβ-dependent and Aβ-independent mechanisms that link Apo-E4 status with AD risk, and consider how to design effective strategies for AD therapy by targeting Apo-E.
Authors:
Chia-Chen Liu; Chia-Chan Liu; Takahisa Kanekiyo; Huaxi Xu; Guojun Bu
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't     Date:  2013-01-08
Journal Detail:
Title:  Nature reviews. Neurology     Volume:  9     ISSN:  1759-4766     ISO Abbreviation:  Nat Rev Neurol     Publication Date:  2013 Feb 
Date Detail:
Created Date:  2013-02-07     Completed Date:  2013-07-08     Revised Date:  2014-01-13    
Medline Journal Info:
Nlm Unique ID:  101500072     Medline TA:  Nat Rev Neurol     Country:  England    
Other Details:
Languages:  eng     Pagination:  106-18     Citation Subset:  IM    
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MeSH Terms
Descriptor/Qualifier:
Alzheimer Disease / epidemiology,  genetics*,  metabolism,  psychology*,  therapy*
Amyloid beta-Peptides / antagonists & inhibitors,  metabolism
Animals
Apolipoproteins E / antagonists & inhibitors,  genetics*,  metabolism,  physiology*
Brain / pathology
Brain Injuries / genetics,  physiopathology
Dementia / genetics,  physiopathology
Dendritic Spines / physiology
Humans
Immunotherapy
Inflammation / genetics,  pathology
Lipid Metabolism / genetics,  physiology
Mild Cognitive Impairment / pathology,  psychology
Neurogenesis / genetics,  physiology
Neuronal Plasticity / genetics,  physiology
Predictive Value of Tests
Risk
Vascular Diseases / genetics,  physiopathology
tau Proteins / metabolism
Grant Support
ID/Acronym/Agency:
P01 AG030128/AG/NIA NIH HHS; P01 NS074969/NS/NINDS NIH HHS; R01 AG021173/AG/NIA NIH HHS; R01 AG027924/AG/NIA NIH HHS; R01 AG031784/AG/NIA NIH HHS; R01 AG035355/AG/NIA NIH HHS; R01 AG038710/AG/NIA NIH HHS; R01 AG044420/AG/NIA NIH HHS
Chemical
Reg. No./Substance:
0/Amyloid beta-Peptides; 0/Apolipoproteins E; 0/tau Proteins
Comments/Corrections
Erratum In:
Nat Rev Neurol. 2013. doi: 10.1038/nmeurol.2013.32
Note: Liu, Chia-Chan [corrected to Liu, Chia-Chen]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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