Europium-Doped Cerium Oxide Nanoparticles for Microglial Amyloid Beta Clearance and Homeostasis

Abstract

Alzheimer's disease (AD) is the most common neurodegenerative disorder. Pathologically, the disease is characterized by the deposition of amyloid beta (Aβ) plaques and the presence of neurofibrillary tangles. These drive microglia neuroinflammation and consequent neurodegeneration. While the means to affect Aβ plaque accumulation pharmacologically was achieved, how it affects disease outcomes remains uncertain. Cerium oxide (CeO₂) reduces Aβ plaques, oxidative stress, inflammation, and AD signs and symptoms. In particular, CeO₂ nanoparticles (CeO₂NPs) induce free-radical-scavenging and cell protective intracellular signaling. This can ameliorate the pathobiology of an AD-affected brain. To investigate whether CeO₂NPs affect microglia neurotoxic responses, a novel formulation of europium-doped CeO₂NPs (EuCeO₂NPs) was synthesized. We then tested EuCeO₂NPs for its ability to generate cellular immune homeostasis in AD models. EuCeO₂NPs attenuated microglia BV2 inflammatory activities after Aβ_1-42 exposure by increasing the cells' phagocytic and Aβ degradation activities. These were associated with increases in the expression of the CD36 scavenger receptor. EuCeO₂NPs facilitated Aβ endolysosomal trafficking and abrogated microglial inflammatory responses. We posit that EuCeO₂NPs may be developed as an AD immunomodulator.