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

Abstract

Alzheimer’s disease (AD) is\nthe most common neurodegenerative\ndisorder. Pathologically, the disease is characterized by the deposition\nof amyloid beta (Aβ) plaques and the presence of neurofibrillary\ntangles. These drive microglia neuroinflammation and consequent neurodegeneration.\nWhile the means to affect Aβ plaque accumulation pharmacologically\nwas achieved, how it affects disease outcomes remains uncertain. Cerium\noxide (CeO₂) reduces Aβ plaques, oxidative stress,\ninflammation, and AD signs and symptoms. In particular, CeO₂ nanoparticles (CeO₂NPs) induce free-radical-scavenging\nand cell protective intracellular signaling. This can ameliorate the\npathobiology of an AD-affected brain. To investigate whether CeO₂NPs affect microglia neurotoxic responses, a novel formulation\nof europium-doped CeO₂NPs (EuCeO₂NPs) was synthesized.\nWe then tested EuCeO₂NPs for its ability to generate cellular\nimmune homeostasis in AD models. EuCeO₂NPs attenuated microglia\nBV2 inflammatory activities after Aβ_1–42 exposure\nby increasing the cells’ phagocytic and Aβ degradation\nactivities. These were associated with increases in the expression\nof the CD36 scavenger receptor. EuCeO₂NPs facilitated Aβ\nendolysosomal trafficking and abrogated microglial inflammatory responses.\nWe posit that EuCeO₂NPs may be developed as an AD immunomodulator.