Magnetite/Ceria Nanoparticle Assemblies for Extracorporeal Cleansing of Amyloid-beta in Alzheimer's Disease

Abstract

Accumulation of amyloid-beta (A beta) peptides in the brain is regarded as a major contributor to the pathogenesis and progression of Alzheimer's disease (AD). However, development of clinically relevant techniques to reduce A beta levels in AD patients is hindered by low efficiency and/or side effects. Here, an extracorporeal A beta cleansing system, where multifunctional magnetite/ceria nanoparticle assemblies are used to remove A beta peptides from flowing blood by specific capture and magnetic separation, is reported. The magnetite nanoparticles in the nanoassembly core enable the magnetic isolation of the captured A beta peptides by generating a large attraction force under an external magnetic field. The ceria nanoparticles in the nanoassembly shell relieve oxidative stress by scavenging reactive oxygen species that are produced by immune response during the process. Blood A beta cleansing treatment of 5XFAD transgenic mice not only demonstrates the decreased A beta levels both in the blood and in the brain but also prevents the spatial working memory deficits, suggesting the potential of the method for AD prevention and therapy.