Oral Exposure to Food‐Grade Nanoparticles Poses a Risk of Alzheimer's Disease‐Like Symptoms by Triggering Autophagy Defects in Neurons

Abstract Preliminary epidemiological studies have revealed a relationship between exposure to environment‐related ultrafine particles and the escalation of Alzheimer's disease (AD). Oral exposure through food is a significant route of human contact with nanoparticles; however, the potential risk of AD induced by food‐grade nanoparticles and the underlying mechanisms remain largely unclear. Here, this study reveals a common mechanism by which food‐grade nanoparticles, including titanium dioxide, nanosilica, and nanosilver, trigger AD‐like pathological changes through epigenetic alterations. Exposure to food‐grade nanoparticles triggers changes in DNA methylation and aberrant ryanodine receptor‐Ca ²⁺ signaling in the mouse brain, contributing to lysosomal impairment and disrupted autophagic flux in neurons. Crucially, these autophagy defects reduced the ability to clear β‐amyloid and pTau proteins, which ultimately accumulated and triggered spatial cognition and memory deficits in mice. In conclusion, this study elucidates the shared toxicological mechanisms induced by different food‐grade nanoparticles, thereby offering valuable insights into ingested nanoparticle exposure and its potential association with neurodegenerative diseases.