Lead-based Perovskite Nanoparticles Exposure Models Sporadic Alzheimer's Disease in Human Cerebral Organoids via SR-BI-Mediated Lipid Metabolism Disruption
Alzheimer's disease is a leading cause of dementia, yet effective therapeutic options remain elusive due to the limitations inherent in existing models, particularly for sporadic AD. Lead based perovskite nanoparticles , which have the potential to release lead, may elevate the risk of developing AD. In this study, we demonstrated that human cerebral organoids exposed to CsPbBr3 nanoparticles, a representative of Pb PNPs, for 15 days exhibited persistent AD like pathologies, including amyloid beta deposition, TAU tangle like aggregates, and compromised neural network activity. Transcriptomic and lipidomic profiling revealed that exposure to CsPbBr3 nanoparticles decreased the expression of SRBI and disrupted lipid metabolism. Remarkably, treatment with the SRBI agonist chenodeoxycholic acid alleviated the AD like pathologies observed in the COs. This study establishes a more relevant model of sporadic AD, providing a promising platform for identifying therapeutic targets and evaluating potential treatments.