Biologically‐inspired ApoE3‐reconstituted high density lipoprotein: toward development of nanomedicines for alzheimer's disease (846.2)

Abstract

Amyloid beta (Aβ) accumulation in the brain plays a central role in Alzheimer’s disease (AD) pathogenesis, and the common late‐onset form of AD is characterized by an overall impairment in Aβ clearance but not in Aβ production. Therefore, development of nanostructures that can facilitate Aβ clearance represents a promising strategy for AD intervention. Here, we hypothesized that biologically‐inspired nanostructure_ApoE3‐reconstituted high density lipoprotein (HDL) (ApoE3‐rHDL) which presents high binding affinity to Aβ might serve as a novel nanomedicine for disease modification in AD by accelerating its clearance. Surface plasmon resonance, transmission electron microscopy and co‐immunoprecipitation analysis showed that ApoE3‐rHDL demonstrated high binding affinity to both Aβ monomer and oligomer. ApoE3‐rHDL also accelerated the microglial, astroglial and liver cell degradation of Aβ by facilitating the lysosome transport pathway. One hour after intravenous administration, about 0.4% ID/g of ApoE3‐rHDL got access to the central nervous system. Four‐week dosing of ApoE3‐rHDL decreased amyloid deposition, attenuated microgliosis, ameliorated neurologic changes and rescued memory deficits in an AD animal model. The findings here indicated that biologically‐inspired nanostructure ApoE3‐rHDL could serve as a novel nanomedicine for disease modification in AD by accelerating its clearance, which also justified the concept that nanostructures with Aβ‐binding affinity might provide a novel nanoplatform for the treatment of AD.Grant Funding Source: This study was supported by National Natural Science Foundation of China (No. 81373351), National K