Vitamin A and vitamin E metabolites comodulate amyloid-β aggregation

Alzheimer’s disease is characterized by the presence in the brain of amyloid plaques formed by the aberrant deposition of the amyloid-β peptide (Aβ). Since many vitamins are dysregulated in this disease, we explored whether these molecules participate in protein homeostasis by modulating Aβ aggregation. By screening 18 fat-soluble and water-soluble vitamins, we found that retinoic acid and α-tocopherol, two metabolites of vitamin A and vitamin E, respectively, affect Aβ aggregation both in vitro and in a C. elegans model of Alzheimer’s disease. We also show that effects of these two vitamin metabolites in combination can cancel each other out, suggesting that the complex composition of the cellular environment could have a protective role against protein aggregation through the simultaneous presence of aggregation promoters and inhibitors. Taken together, these results indicate that vitamins and their metabolites may be added to the list of components of the quality control system that regulate protein aggregation.