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

Apolipoprotein E (apoE) alleles determine the age-adjusted relative risk (e psilon 4 > epsilon 3) for Alzheimer's disease (AD). ApoE may affect AD path ogenesis by promoting deposition of the amyloid-beta (A beta) peptide and i ts conversion to a fibrillar form. To determine the effect of apoE on A bet a deposition and AD pathology, we compared App(V717F) transgenic (TG) mice expressing mouse, human, or no apoE (apoE(-/-)). A severe, plaque-associate d neuritic dystrophy developed in App(V717F) TG mice expressing mouse or hu man apoE. Though significant levels of A beta deposition also occurred in A pp(V717F) TG, apoE(-/-) mice, neuritic degeneration was virtually absent, E xpression of apoE3 and apoE4 in App(V717F) TG, apoE(-/-) mice resulted in f ibrillar A beta deposits and neuritic plaques by 15 months of age and subst antially (> 10-fold) more fibrillar deposits were observed in apoE4-express ing App(V717F) TC mice. Our data demonstrate a critical and isoform-specifi c role for apoE in neuritic plaque formation, a pathological hallmark of AD .