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

Inhibition of amyloid-β (Aβ) aggregation is an attractive therapeutic strategy for treatment of Alzheimer's disease (AD). We previously reported that vitamin A and β-carotene inhibit fibrillation of Aβ₄₀ and Aβ₄₂ (Ono et al, 2004, Exp Neurol). In this study, we firstly examined the effects of vitamin A (retinoic acid, retinol, and retinal), β-carotene, vitamin B2, vitamin B6, vitamin C, vitamin E, coenzyme Q10, and α-lipoic acid on oligomerization of Aβ₄₀ and Aβ₄₂ in vitro; vitamin A and β-carotene dose-dependently inhibited oligomerization of Aβ₄₀ and Aβ₄₂. Furthermore, retinoic acid decreased cellular toxicity by inhibition of Aβ₄₂ oligomerization. Second, we analyzed how vitamin A inhibits Aβ aggregation by using fluorescence spectroscopy and thioflavin T assay with two Aβ fragments, Aβ_1-16 and Aβ_25-35. A fluorescence peak of retinoic acid was greatly restrained in the presence of Aβ_25-35, and retinoic acid inhibited aggregation of Aβ_25-35, but not of Aβ_1-16, which suggest the specific binding of retinoic acid to the C-terminal portion of Aβ. Thus, vitamin A and β-carotene might be key molecules for prevention of AD.