RESUMO
Alzheimer's disease (AD) is characterized by the formation of extracellular amyloid plaques containing the amyloid ß-protein (Aß) within the parenchyma of the brain. Aß42, which is 42 amino acids in length, is considered to be the key pathogenic factor in AD. Iron deposition is found abundantly in the amyloid plaques of AD patients; however, whether iron intake exacerbates amyloid deposition in vivo is unknown. Here, we treated AD model mice with iron-containing water and found that Aß42 deposition in the brain was significantly inhibited, along with a decrease in iron deposition. Iron treatment did not change the overall levels of iron in the brain or serum. Interestingly, Aß40 generation was significantly increased by iron treatment in amyloid precursor protein (APP)-overexpressing fibroblasts, whereas Aß42 generation did not change, which led to a decreased Aß42/Aß40 ratio. Because Aß40 can inhibit Aß42 aggregation in vitro, and Aß40 inhibits amyloid formation in vivo, our results suggest that iron can selectively enhances Aß40 generation and inhibit amyloid deposition by reducing the Aß42/Aß40 ratio. Thus, iron may be used as a novel treatment for reducing the Aß42/Aß40 ratio and Aß42 deposition in AD.
