Chronic Starch-Based Microplastic Exposure Enhances the Risk of Alzheimer's Disease in Mice by Perturbing the Gut-Brain Axis.

The potential neurotoxicity of biomicroplastics has attracted increasing attention with the global expansion of bioplastics. Our recent findings revealed that starch-based microplastics (SB-MPs) can disrupt fatty acid metabolism, a perturbation strongly linked to neurotoxicity disorders. However, systematic investigations into the neurotoxic potential of chronic SB-MP exposure and its underlying mechanisms remain scarce, limiting comprehensive risk assessment. Here, we exposed mice to food-relevant concentrations of SB-MPs for 180 days and evaluated the risk of Alzheimer's disease (AD). SB-nanoparticles (SB-NPs) were found in the brain, accompanied by significantly impaired locomotor activity, learning, and memory, while increasing cerebral Aβ-42 protein levels, indicating a strong potential to promote AD-like pathology. Multiomics integration further revealed that SB-MPs are driving the expansion of bacterial taxa and metabolic pathways associated with short-chain fatty acid (SCFA) production. The resulting SCFAs overload and SB-NPs entered circulation and accumulated in brain tissue, where they disturbed fatty acid homeostasis and provoked neuroinflammation, ultimately increasing AD risk. Collectively, these findings demonstrate that chronic exposure to SB-MPs can elevate AD risk by perturbing the gut-brain axis. Continued research is needed to clarify the neurotoxicity of SB-MPs and to inform the design of greener bioplastics with reduced health impacts.