Mechanistic Evidence Mapping Ochratoxin A Toxicity onto Alzheimer’s Disease-Relevant Neurodegenerative Pathways: A Systematic Review of Experimental Models

Ochratoxin A (OTA) is a prevalent foodborne mycotoxin that has been increasingly recognized as a potential environmental contributor to neurodegenerative diseases. Despite extensive research, a systematic integration of how OTA replicates the specific pathological hallmarks of Alzheimer’s Disease (AD) is currently lacking. This study provides a comprehensive systematic review of the mechanistic evidence linking OTA exposure to AD-related pathways, utilizing the Adverse Outcome Pathway (AOP) framework to categorize complex toxicological data into biological key events (KEs). A systematic literature search was conducted across PubMed, Scopus, and Web of Science. A total of 24 peer-reviewed articles were selected for synthesis, comprising 14 in vitro studies and 10 in vivo investigations. The integrated evidence demonstrates that OTA exposure triggers a robust toxicological cascade that replicates several key mechanistic pathways associated with AD in experimental models. Early molecular triggers involve significant redox imbalance and mitochondrial bioenergetic failure, which serve as catalysts for sustained neuroinflammation and microglial activation. In vivo data, from multiple animal models, consistently show that these cellular dysfunctions culminate in structural damage. This systematic integration provides a clearer roadmap for future risk assessment and emphasizes the urgent need for refined regulatory guidelines to protect neurological health from chronic mycotoxin exposure.