Spermidine protects mitochondria against amyloid-β oligomers

Background Alzheimer's disease (AD) is a neurodegenerative condition characterized by amyloid-β (Aβ) plaques in the brain. In early pathological conditions, Aβ oligomers localize in mitochondria to promote disease progression by causing mitochondrial dysfunction. Objective Establish a robust AD pathological in vitro model and assess the therapeutic effect of spermidine (SPD) against extracellular Aβ oligomers. Methods In this study, high-resolution respirometry, flow cytometry, and immunoblotting techniques were used to characterize the negative effects of Aβ oligomer localization in mitochondria and assess the potential neuroprotective effects of SPD. Results Oligomeric Aβ accumulates in and causes mitochondrial dysfunction, as evidenced by increased mitochondrial superoxide production, decreased mitochondrial mass, and decreased maximal mitochondrial respiration and spare reserve capacity. SPD, an endogenously produced polyamine that can also be provided through exogenous supplementation, improved these markers and protected mitochondria of oligomer-treated cells. Conclusions SPD ameliorated mitochondrial dysfunction caused by Aβ oligomers in vitro.