P1‐222: Vitamin A has anti‐oligomerization effects on Aβ in vitro

Inhibition of amyloid- (A) aggregation is an attractive therapeutic strategy for treatment of Alzheimer's disease (AD). We previously reported that vitamin A and -carotene inhibit fibrillation of A40 and A42 (Ono et al, 2004, Exp Neurol). In this study, we firstly examined the effects of vitamin A (retinoic acid, retinol, and retinal), -carotene, vitamin B2, vitamin B6, vitamin C, vitamin E, coenzyme Q10, and -lipoic acid on oligomerization of A40 and A42 in vitro; vitamin A and -carotene dose-dependently inhibited oligomerization of A40 and A42. Furthermore, retinoic acid decreased cellular toxicity by inhibition of A42 oligomerization. Second, we analyzed how vitamin A inhibits A aggregation by using fluorescence spectroscopy and thioflavin T assay with two A fragments, A1-16 and A25-35. A fluorescence peak of retinoic acid was greatly restrained in the presence of A25-35, and retinoic acid inhibited aggregation of A25-35, but not of A1-16, which suggest the specific binding of retinoic acid to the C-terminal portion of A. Thus, vitamin A and -carotene might be key molecules for prevention of AD.