Apolipoprotein E isoform-dependent amyloid deposition and neuritic degeneration in a mouse model of Alzheimer's disease.

TitleApolipoprotein E isoform-dependent amyloid deposition and neuritic degeneration in a mouse model of Alzheimer's disease.
Publication TypeJournal Article
Year of Publication2000
AuthorsHoltzman DM, Bales KR, Tenkova T, Fagan AM, Parsadanian M, Sartorius LJ, Mackey B, Olney J, McKeel D, Wozniak D, Paul SM
JournalProc Natl Acad Sci U S A
Volume97
Issue6
Pagination2892-7
Date Published2000 Mar 14
ISSN0027-8424
KeywordsAlzheimer Disease, Animals, Apolipoproteins E, Disease Models, Animal, Genetic Predisposition to Disease, Hippocampus, Humans, Mice, Mice, Inbred C57BL, Mice, Inbred DBA, Mice, Transgenic, Nerve Degeneration, Neurites, Plaque, Amyloid, Protein Isoforms, Thiazoles, Time Factors
Abstract

Apolipoprotein E (apoE) alleles determine the age-adjusted relative risk (epsilon4 > epsilon3) for Alzheimer's disease (AD). ApoE may affect AD pathogenesis by promoting deposition of the amyloid-beta (Abeta) peptide and its conversion to a fibrillar form. To determine the effect of apoE on Abeta deposition and AD pathology, we compared APP(V717F) transgenic (TG) mice expressing mouse, human, or no apoE (apoE(-/-)). A severe, plaque-associated neuritic dystrophy developed in APP(V717F) TG mice expressing mouse or human apoE. Though significant levels of Abeta deposition also occurred in APP(V717F) TG, apoE(-/-) mice, neuritic degeneration was virtually absent. Expression of apoE3 and apoE4 in APP(V717F) TG, apoE(-/-) mice resulted in fibrillar Abeta deposits and neuritic plaques by 15 months of age and substantially (>10-fold) more fibrillar deposits were observed in apoE4-expressing APP(V717F) TG mice. Our data demonstrate a critical and isoform-specific role for apoE in neuritic plaque formation, a pathological hallmark of AD.

DOI10.1073/pnas.050004797
Alternate JournalProc. Natl. Acad. Sci. U.S.A.
PubMed ID10694577
PubMed Central IDPMC16026
Grant ListAG13956 / AG / NIA NIH HHS / United States