Dynein-Dependent Endo-Lysosomal Degradation Drives Lewy Body Disorders Accompanied by Aβ Pathology.

ABSTRACT: Dementia with Lewy bodies (DLB) is a significant cause of dementia. However, the limited availability of animal and cellular models that accurately replicate early DLB pathogenesis hampers the understanding of how Aβ plaques influence α-synuclein (αSyn) pathologies. This study addresses this gap by co-culturing primary neurons with adult hippocampal brain slices from either wild-type or Alzheimer's disease (AD) mice containing abundant Aβ plaques and cytokines. Neurons exposed to AD slices showed impaired dynein-dependent organelle trafficking, reducing endosome-lysosome fusion and causing defective degradation of amyloidogenic αSyn fibrils, thus increasing αSyn inclusions. Notably, an abnormal pre-accumulation of dynein in AD mice suggests that dysfunctional dynein may serve as a nucleati

SUBMITTER: Zhou L 

PROVIDER: S-EPMC12499460 | biostudies-literature | 2025 Oct

REPOSITORIES: biostudies-literature