Alzheimer's disease (AD) is characterized by the formation of extracellular amyloid plaques containing the amyloid beta-protein (A beta) within the parenchyma of the brain. A beta 42, 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 A beta 42 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, A beta 40 generation was significantly increased by iron treatment in amyloid precursor protein (APP)-overexpressing fibroblasts, whereas A beta 42 generation did not change, which led to a decreased A beta 42/A beta 40 ratio. Because A beta 40 can inhibit A beta 42 aggregation in vitro, and A beta 40 inhibits amyloid formation in vivo, our results suggest that iron can selectively enhances A beta 40 generation and inhibit amyloid deposition by reducing the A beta 42/A beta 40 ratio. Thus, iron may be used as a novel treatment for reducing the A beta 42/A beta 40 ratio and A beta 42 deposition in AD. (C) 2019 Elsevier Inc. All rights reserved.