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.