Apolipoprotein E in Alzheimer's disease and other neurological disorders

Philip B. Verghese, Joseph M. Castellano, David M. Holtzman

Research output: Contribution to journalReview article

459 Scopus citations

Abstract

Apolipoprotein E (APOE) is a 299-aminoacid protein encoded by the APOE gene. Three common polymorphisms in the APOE gene, e{open}2, e{open}3, and e{open}4, result in a single aminoacid change in the APOE protein. APOE e{open}2, e{open}3, and e{open}4 alleles strongly alter, in a dose-dependent manner, the likelihood of developing Alzheimer's disease and cerebral amyloid angiopathy. In particular, APOE e{open}4 is associated with increased risk for Alzheimer's disease whereas APOE e{open}2 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 e{open}4 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.

Original languageEnglish
Pages (from-to)241-252
Number of pages12
JournalThe Lancet Neurology
Volume10
Issue number3
DOIs
StatePublished - Mar 1 2011

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