Breast carcinoma amplified sequence 2 rescues adult hippocampal neurogenesis and cognitive deficits in Alzheimer’s disease via regulating BDNF/TrkB signaling

In Alzheimer’s disease (AD), AHN is impeded, while the molecular basis behind this impairment remains to be elucidated. Here we identified Breast carcinoma amplified sequence 2 (BCAS2), a core component of the CDC5L/Prp19 spliceosome complex, regulating AHN in AD.

Using Bcas2 conditional knockout mice, AD mouse model APP/PS1 mice, established mouse primary adult neural stem cells and single cell sequencing, we demonstrate that BCAS2 replacement in adult mouse hippocampus promotes NSC activation and differentiation to neuron, restore AHN and relevant memory deficits through BDNF/TrkB signaling. Our findings corroborate the significance of AHN in AD and reveal the possible therapeutic potential of targeting BCAS2 in neurodegeneration.