Deferoxamine enhances alternative activation of microglia and inhibits amyloid beta deposits in APP/PS1 mice.

The neurotoxicity of amyloid-β peptide (Aβ), a predominant histopathological hallmark lesion of Alzheimer's disease (AD), is enhanced by iron, as found in amyloid plaques of Alzheimer's disease (AD) patients. We investigated whether deferoxamine (DFX) treatment promotes functional recovery and tissue repair in APP/PS1 double transgenic mice. Twelve-month-old APP/PS1 mice were randomly divided into two groups (APP/PS1 and DFX). Neurological deficits were monitored for 2weeks following DFX treatment. To characterize the activation of the microglia, expression of the M1 and M2 phenotypes was analyzed by immunohistochemistry and immunoblotting. Moreover, deposition of iron and Aβ, as well as apoptosis, were examined, and a behavioral test was performed. DFX significantly ameliorated cognitive function and deposition of Aβ as well as inhibited apoptosis in the brain. Consistent with these observations, DFX induced M2 activation of microglia and inhibited M1 activation of microglia in the hippocampus of APP/PS1 mice. In conclusion, DFX treatment improved functional recovery of AD mice, and the mechanism may involve DFX-induced M2 activation of microglia.