Vitamin A has Anti-Oligomerization Effects on Amyloid-beta In Vitro

Inhibition of amyloid-beta (A beta) aggregation is an attractive therapeutic strategy for treatment of Alzheimer's disease (AD). We previously reported that vitamin A and beta-carotene inhibit fibrillation of A beta(40) and A beta(42) (Ono et al, 2004, Exp Neurol). In this study, we firstly examined the effects of vitamin A (retinoic acid, retinol, and retinal), beta-carotene, vitamin B2, vitamin B6, vitamin C, vitamin E, coenzyme Q10, and alpha-lipoic acid on oligomerization of A beta(40) and A beta(42) in vitro; vitamin A and beta-carotene dose-dependently inhibited oligomerization of A beta(40) and A beta(42). Furthermore, retinoic acid decreased cellular toxicity by inhibition of A beta 42 oligomerization. Second, we analyzed how vitamin A inhibits A beta aggregation by using fluorescence spectroscopy and thioflavin T assay with two A beta fragments, A beta(1-16) and A beta(25-35). A fluorescence peak of retinoic acid was greatly restrained in the presence of A beta(25-35), and retinoic acid inhibited aggregation of A beta(25-35), but not of A beta 1-16, which suggest the specific binding of retinoic acid to the C-terminal portion of A beta. Thus, vitamin A and beta-carotene might be key molecules for prevention of AD.