Expression of human apolipoprotein E reduces amyloid-beta deposition in a mouse model of Alzheimer's disease.

TitleExpression of human apolipoprotein E reduces amyloid-beta deposition in a mouse model of Alzheimer's disease.
Publication TypeJournal Article
Year of Publication1999
AuthorsHoltzman DM, Bales KR, Wu S, Bhat P, Parsadanian M, Fagan AM, Chang LK, Sun Y, Paul SM
JournalJ Clin Invest
Date Published1999 Mar
KeywordsAlzheimer Disease, Amyloid beta-Peptides, Animals, Apolipoproteins E, Disease Models, Animal, Humans, Mice, Mice, Transgenic, Mutation, Protein Isoforms, Recombinant Proteins

The epsilon4 allele of apolipoprotein E (apo E) is associated with an increased risk for developing Alzheimer's disease (AD). This may be due to interactions between apo E and the amyloid-beta protein (Abeta). To assess the effects of human apo E isoforms on Abeta deposition in vivo, we bred apo E3 and apo E4 hemizygous (+/-) transgenic mice expressing apo E by astrocytes to mice homozygous (+/+) for a mutant amyloid precursor protein (APPV717F) transgene that develop age-dependent AD neuropathology. All mice were on a mouse apo E null (-/-) background. By nine months of age, APPV717F+/-, apo E-/- mice had developed Abeta deposition, and, as reported previously, the quantity of Abeta deposits was significantly less than that seen in APPV717F+/- mice expressing mouse apo E. In contrast to effects of mouse apo E, similar levels of human apo E3 and apo E4 markedly suppressed early Abeta deposition at nine months of age in APPV717F+/- transgenic mice, even when compared with mice lacking apo E. These findings suggest that human apo E isoforms decrease Abeta aggregation or increase Abeta clearance relative to an environment in which mouse apo E or no apo E is present. The results may have important implications for understanding mechanisms underlying the link between apo E and AD.

Alternate JournalJ. Clin. Invest.
PubMed ID10079115
PubMed Central IDPMC408154
Grant ListAG-13956 / AG / NIA NIH HHS / United States
AG00861 / AG / NIA NIH HHS / United States