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PMID: 21349439 Published · ppublish English Journal Article Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't Review

Apolipoprotein E in Alzheimer's disease and other neurological disorders.

The Lancet. Neurology ·Vol. 10 ·No. 3 ·2011-03-00 ·Pages 241-52

Verghese PB, Castellano JM, Holtzman DM

Abstract

Apolipoprotein E (APOE) is a 299-aminoacid protein encoded by the APOE gene. Three common polymorphisms in the APOE gene, ɛ2, ɛ3, and ɛ4, result in a single aminoacid change in the APOE protein. APOE ɛ2, ɛ3, and ɛ4 alleles strongly alter, in a dose-dependent manner, the likelihood of developing Alzheimer's disease and cerebral amyloid angiopathy. In particular, APOE ɛ4 is associated with increased risk for Alzheimer's disease whereas APOE ɛ2 is associated with decreased risk. The effects of APOE genotype on risk of these diseases are likely to be mediated by differential effects of APOE on amyloid-β accumulation in the brain and its vasculature. Response to treatment for Alzheimer's disease might differ according to APOE genotype. Because convincing evidence ties the APOE genotype to risk of Alzheimer's disease and cerebral amyloid angiopathy, APOE has been studied in other neurological diseases. APOE ɛ4 is associated with poor outcome after traumatic brain injury and brain haemorrhage, although the mechanisms underlying these associations are unclear. The possibility that APOE has a role in these and other neurological diseases has been of great interest, but convincing associations have not yet emerged.

MeSH Terms
Alzheimer Disease/diagnosis,genetics Animals Apolipoproteins E/genetics Humans Nervous System Diseases/diagnosis,genetics Polymorphism, Genetic/genetics
Chemicals
Apolipoproteins E
Authors & Affiliations
3 authors, click to expand affiliations / ORCID
Verghese Philip B
Department of Neurology, Hope Center for Neurological Disorders, and the Knight Alzheimer's Disease Research Center, Washington University School of Medicine, St Louis, MO, USA.
Castellano Joseph M
Holtzman David M
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Article Info
Journal
The Lancet. Neurology
Abbr.
Lancet Neurol
ISSN
1474-4465
DOI
10.1016/S1474-4422(10)70325-2
Published
2011-03-00
Pages
241-52
Language
English
Region
England
NLM ID
101139309
PMCID
PMC3132088
Subset
IM
Grants
NINDS NIH HHS · R37 NS034467 · United States
NIA NIH HHS · R01 AG013956 · United States
NIA NIH HHS · AG13956 · United States
NIA NIH HHS · R37 AG013956 · United States
NIA NIH HHS · AG026276 · United States
NIA NIH HHS · AG034004 · United States
NIA NIH HHS · R37 AG013956-16 · United States
NIA NIH HHS · AG03991 · United States
NIA NIH HHS · P01 AG003991 · United States
NIA NIH HHS · P50 AG005681 · United States
NINDS NIH HHS · NS034467 · United States
NIA NIH HHS · P01 AG026276 · United States
NINDS NIH HHS · R01 NS034467 · United States
NIA NIH HHS · F31 AG034004 · United States
NIA NIH HHS · F31 AG034004-04 · United States
External Links
PubMed source DOI: 10.1016/S1474-4422(10)70325-2 PMC Full Text View journal details
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