Europium-Doped Cerium Oxide Nanoparticles for MicroglialAmyloid Beta Clearance and Homeostasis

Alzheimer's disease (AD) is the most common neuro-degenerative disorder. Pathologically, the disease is characterized by thedeposition of amyloid beta (A beta) plaques and the presence of neurofibrillarytangles. These drive microglia neuroinflammation and consequent neuro-degeneration. While the means to affect A beta plaque accumulationpharmacologically was achieved, how it affects disease outcomes remainsuncertain. Cerium oxide (CeO2) reduces A beta plaques, oxidative stress,inflammation, and AD signs and symptoms. In particular, CeO2nanoparticles (CeO2NPs) induce free-radical-scavenging and cell protectiveintracellular signaling. This can ameliorate the pathobiology of an AD-affected brain. To investigate whether CeO2NPs affect microglia neurotoxicresponses, a novel formulation of europium-doped CeO2NPs (Eu-CeO2NPs) was synthesized. We then tested EuCeO2NPs for its ability togenerate cellular immune homeostasis in AD models. EuCeO2NPsattenuated microglia BV2 inflammatory activities after A beta 1-42exposureby increasing the cells'phagocytic and A beta degradation activities. These were associated with increases in the expression of the CD36scavenger receptor. EuCeO2NPs facilitated A beta endolysosomal trafficking and abrogated microglial inflammatory responses. We positthat EuCeO2NPs may be developed as an AD immunomodulator.