Mild magnetic nanoparticle hyperthermia promotes the disaggregation and microglia-mediated clearance of beta-amyloid plaques.

The formation of beta-amyloid (Aβ) plaques is a classical hallmark of Alzheimer's disease (AD) that is associated with the promotion of neuroinflammation and subsequent neurotoxicity. Given the limited therapeutic options for targeting and clearing Aβ plaques in AD, there is an urgent need to develop effective approaches to reduce plaque accumulation. The objective of this study was to validate mild magnetic nanoparticle (MNP) hyperthermia technology as a strategy to clear Aβ deposits and determine the impact on microglia functionality. Our results demonstrated that the heating of MNPs localized to Aβ aggregates upon exposure to high frequency alternating magnetic field (AMF) was sufficient to disrupt Aβ plaques, resulting in its fragmentation. Importantly, this could facilitate the phagocytic clearance of Aβ as well as attenuate pro-inflammatory responses by human microglial cells. Our results support the feasibility of mild MNP/AMF hyperthermia as a new strategy for reducing beta-amyloid burdens in Alzheimer's disease.