Incidental vs. engineered nanoparticles in Alzheimer’s and Parkinson’s disease: Pathological pathways and therapeutic interventions

Nanoparticles (NPs) play dual roles in neurodegeneration. Incidental NPs, generated unintentionally from environmental and industrial sources, are linked to oxidative stress, neuroinflammation, and disruption of the blood-brain barrier in Alzheimer's disease (AD) and Parkinson's disease (PD). Engineered NPs are designed for diagnosis and therapy using nanobodies, nanozymes, and other engineered nanoparticle (ENP) platforms that enable targeted delivery, modulation of neuroimmune pathways, and interference with pathological protein aggregation. This review aligns source-based classes (incidental versus engineered) with composition-based families (metal-based, carbon-based, and polymeric or inorganic), and summarizes routes of exposure, mechanistic toxicology, and engineered interventions relevant to AD and PD. We also evaluate current limitations, including biocompatibility, relevance to chronic exposure, and clinical benchmarking, and we outline priorities for translating nanotechnology into practical diagnostics and therapeutics for neurodegenerative disease.