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A feasibility study for the application of magnetic hyperthermia towards the clearance of beta-amyloids in mouse model of Alzheimer’s Disease

Min-Ho Kim, Ph.D., Biological Sciences, С»ÆƬÊÓƵ

Woo-Yang Kim, Ph.D., Biological Sciences, С»ÆƬÊÓƵ

Alzheimer's disease (AD) is a devastating neurodegenerative disorder characterized by progressive impairment of memory and cognitive functions. Many lines of genetic and biochemical evidence strongly highlight a central role of the amyloid pathway in the pathogenesis of AD where abnormal accumulation of amyloid beta (Aβ) into extracellular toxic plaques is responsible for neurodegeneration and resulting dementia in AD. Given that numerous pharmacological strategies targeting Ab have failed in recent clinical trials or limited success in mid- to late-stage clinical development, an alternative and innovative strategy to eliminate Aβ plaques is urgently needed. Our long-term goal is to develop a minimally invasive, non-pharmacological strategy to remove toxic Aβ plaques by utilizing targeted magnetic hyperthermia towards the treatment of AD/ADRD. The principal of this strategy is to target Aβ plaques with biocompatible magnetic nanoparticles (MNPs) and remotely activate the MNPs with the application of alternating magnetic field (AMF). Our preliminary data from an in vitro study demonstrated that mild MNP/AMF hyperthermia applied at a safe thermal dose was sufficient to disrupt Aβ plaques, whose clearance was facilitated by microglial cells. The immediate goal of this proposal is to test the feasibility of applying mild MNP/AMF as a potential treatment for AD by using a mouse model in vivo. In this study, we will determine the range of thermal dose that can be safely applied to a brain tissue without eliciting significant toxic effects to brain functioning in a mouse model.