Human apolipoprotein E2 promotes parenchymal amyloid deposition and neuronal loss in vasculotropic mutant amyloid-β protein Tg-SwDI mice.

摘要: Human apolipoprotein (ApoE) genotype influences the development of Alzheimer's disease and cerebral amyloid angiopathy (CAA), where e4 allele increases e2 decreases risk for developing disease. Specific mutations within amyloid-β (Aβ) peptide have been identified that cause familial forms CAA. However, influence APOE on accumulation CAA mutant Aβ in brain is not well understood. Earlier, we showed human ApoE4 redistributes fibrillar deposition from microvasculature to parenchymal plaques Tg-SwDI mice, a model accumulates Dutch/Iowa (E22Q/D23N) (Xu et al., J Neurosci 28, 5312-5320, 2008). ApoE2 can reduce pathology transgenic models plaques. Here determined if location severity mice. Comparing mice bred onto APOE2/2 or APOE4/4 background, found there was no change levels total Aβ(40) Aβ(42) compared endogenous mouse background. In either similarly strong reduction microvascular emergence extensive plaque amyloid. both Tg-SwDI-hAPOE2/2 Tg-SwDI-hAPOE4/4 distribution ApoE proteins neuronal loss were associated with These findings suggest ApoE4, does beneficially quantitative spatial