Spermidine reduces neuroinflammation and soluble amyloid beta in an Alzheimer’s disease mouse model

Deposition of amyloid beta (Aβ) and hyperphosphorylated tau along with glial cell-mediated neuroinflammation are prominent pathogenic hallmarks of Alzheimer’s disease (AD). In recent years, impairment of autophagy has been found to be another important feature contributing to AD progression. Therefore, the potential of the autophagy activator spermidine, a small body-endogenous polyamine often used as dietary supplement, was assessed on Aβ pathology and glial cell-mediated neuroinflammation. Oral treatment of the amyloid prone AD-like APPPS1 mice with spermidine reduced neurotoxic soluble Aβ and decreased AD-associated neuroinflammation. A subsequent proteome analysis of isolated microglia confirmed the anti-inflammatory and revealed cytoskeletal effects of spermidine in APPPS1 mice. Our data highlight that the autophagy activator spermidine holds the potential to enhance Aβ degradation and to counteract microglia-mediated neuroinflammation in AD pathology.