Title | Apolipoprotein E isoform-dependent amyloid deposition and neuritic degeneration in a mouse model of Alzheimer's disease. |
Publication Type | Journal Article |
Year of Publication | 2000 |
Authors | Holtzman DM, Bales KR, Tenkova T, Fagan AM, Parsadanian M, Sartorius LJ, Mackey B, Olney J, McKeel D, Wozniak D, Paul SM |
Journal | Proc Natl Acad Sci U S A |
Volume | 97 |
Issue | 6 |
Pagination | 2892-7 |
Date Published | 2000 Mar 14 |
ISSN | 0027-8424 |
Keywords | Alzheimer 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. |
DOI | 10.1073/pnas.050004797 |
Alternate Journal | Proc. Natl. Acad. Sci. U.S.A. |
PubMed ID | 10694577 |
PubMed Central ID | PMC16026 |
Grant List | AG13956 / AG / NIA NIH HHS / United States |