Main content area

Iron treatment inhibits Aβ42 deposition in vivo and reduces Aβ42/Aβ40 ratio

Shen, Xuefeng, Liu, Junjun, Fujita, Yu, Liu, Shuyu, Maeda, Tomoji, Kikuchi, Kota, Obara, Toshiki, Takebe, Arisa, Sayama, Rieko, Takahashi, Tomoko, Matsue, Ai, Sera, Koichiro, Michikawa, Makoto, Komano, Hiroto, Zou, Kun
Biochemical and biophysical research communications 2019 v.512 no.4 pp. 653-658
Alzheimer disease, amino acids, amyloid, blood serum, brain, fibroblasts, iron, patients
Alzheimer's disease (AD) is characterized by the formation of extracellular amyloid plaques containing the amyloid β-protein (Aβ) within the parenchyma of the brain. Aβ42, 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 Aβ42 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, Aβ40 generation was significantly increased by iron treatment in amyloid precursor protein (APP)-overexpressing fibroblasts, whereas Aβ42 generation did not change, which led to a decreased Aβ42/Aβ40 ratio. Because Aβ40 can inhibit Aβ42 aggregation in vitro, and Aβ40 inhibits amyloid formation in vivo, our results suggest that iron can selectively enhances Aβ40 generation and inhibit amyloid deposition by reducing the Aβ42/Aβ40 ratio. Thus, iron may be used as a novel treatment for reducing the Aβ42/Aβ40 ratio and Aβ42 deposition in AD.