Synaptic adhesion molecule protocadherin-γC5 mediates β-amyloid-induced neuronal hyperactivity and cognitive deficits in Alzheimer's disease.

Neuronal hyperactivity induced by β-amyloid (Aβ) is an early pathological feature in Alzheimer's disease (AD) and contributes to cognitive decline in AD progression. However, the underlying mechanisms are still unclear. Here, we revealed that Aβ increased the expression level of synaptic adhesion molecule protocadherin-γC5 (Pcdh-γC5) in a Ca-dependent manner, associated with aberrant elevation of synapses in both Aβ-treated neurons in vitro and the cortex of APP/PS1 mice in vivo.