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However, the limited availability of animal and cellular models that accurately replicate early DLB pathogenesis hampers the understanding of how A\u03b2 plaques influence \u03b1\u2010synuclein (\u03b1Syn) pathologies. This study addresses this gap by co\u2010culturing primary neurons with adult hippocampal brain slices from either wild\u2010type or Alzheimer's disease (AD) mice containing abundant A\u03b2 plaques and cytokines. Neurons exposed to AD slices showed impaired dynein\u2010dependent organelle trafficking, reducing endosome\u2013lysosome fusion and causing defective degradation\u00a0of amyloidogenic \u03b1Syn fibrils,\u00a0thus increasing\u00a0\u03b1Syn inclusions. Notably, an abnormal pre\u2010accumulation of dynein in AD mice suggests that dysfunctional dynein may serve as a nucleation site for \u03b1Syn aggregation upon exposure to pathogenic fibrils. 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