Oxidative stress has been found to be associated with the progression of neurodegenerative diseases such as Alzheimer's, Parkinson's, Lou Gehrig's, etc. In the recent years, cerium oxide nanoparticles (CNPs) have been studied as potent antioxidant agents able to exert neuroprotective effects. This work reports polyethylene glycol (PEG)-coated and antibody-conjugated CNPs for the selective delivering to Aβ aggregates, and the protective effect against oxidative stress/Aβ-mediated neurodegeneration. In this study PEG-coated and anti-Aβ antibody-conjugated antioxidant nanoparticles (Aβ-CNPs-PEG) were developed, and their effects on neuronal survival and brain-derived neurotrophic factor (BDNF) signaling pathway were examined. Aβ-CNPs-PEG specifically targets the Aβ aggregates, and concomitant rescue of neuronal survival better than Aβ-CNPs, by modulating the BDNF signaling pathway. This proof of concept work may allow in the future, once validated in vivo, for the selective delivery of CNPs only to affected brain areas.