Disruption in Proteostasis, Microglia‐mediated Synapse pruning, and Neuronal populations in BSN P3866A knock‐in Mouse model of Neurodegeneration

Our BSNKI mouse model revealed the contributions of BSN P3866A mutation to tau pathogenesis and neurodegeneration. BSNKI animals displayed progressive motor and memory impairments, deposits of endogenous tau and BSN, as well as changes in gene expression and neuronal populations. Notably, BSN likely plays a dual role, promoting tau aggregation and sequestering protein degradation molecules, leading to tau and protein accumulation at the soma and synapse, which in turn could trigger neuroinflammation and other cellular changes. These findings propose BSN as a promising therapeutic target for tauopathies, underscoring the need for further exploration to elucidate underlying mechanisms and therapeutic implications.