(95c) Magnetothermal Disaggregation of Amyloid-? Plaques and Tau Tangles

Tauopathies are a spectrum of neurogenerative disorders associated with Alzheimer’s disease, Parkinson’s disease, and Chronic Traumatic Encephalopathy. Tauopathies are characterized by the accumulation of tau tangles, and may also present with another abnormal protein like amyloid-β plaques[1]. These pathogenic proteins induce neuronal dysfunction and death; no treatments currently exist that reduce the disease progression. It is hypothesized that disaggregating these pathogenic proteins could prevent disease progression. We propose that functionalized Magnetic Iron-Oxide Nanoparticles (MNPs) can target the pathogenic proteins, disaggregate the plaques, and release therapeutic agents via a physiologically safe alternating magnetic field (AMF). In this study, we will first develop an in vitro model to elucidate amyloid-β plaques and tau tangles within neural networks. Then, we will investigate the magnetothermal disaggregation of these protein plaques using the developed in vitro model. Up to today, we have successfully studied the kinetics of aggregation of amyloid-β in solution and in vitro. We have replicated pathogenic amyloid-β and tau aggregates in vitro utilizing primary hippocampal neurons and neurons differentiated from neuroblastoma cells (SH-SY5Y). MNPs have been synthesized and characterized through dynamic light scattering and electron microscopy, and functionalized to target the pathogenic proteins. The AMF induced hysteretic heat dissipation of MNPs will be optimized to induce disaggregation of the pathogenic proteins and deliver therapeutic agents within the in vitro models. In future studies this model will be utilized to disaggregate the amyloid-β plaques through magnetic hyperthermia. This study will aid us in the development of non-invasive treatments for tauopathies.