Neurogenic effects of β-amyloid in the choroid plexus epithelial cells in Alzheimer's disease

beta-amyloid (A beta) can promote neurogenesis, both in vitro and in vivo, by inducing neural progenitor cells to differentiate into neurons. The choroid plexus in Alzheimer's disease (AD) is burdened with amyloid deposits and hosts neuronal progenitor cells. However, neurogenesis in this brain tissue is not firmly established. To investigate this issue further, we examined the effect of A beta on the neuronal differentiation of choroid plexus epithelial cells in several experimental models of AD. Here we show that A beta regulates neurogenesis in vitro in cultured choroid plexus epithelial cells as well as in vivo in the choroid plexus of APP/Ps1 mice. Treatment with oligomeric A beta increased proliferation and differentiation of neuronal progenitor cells in cultured choroid plexus epithelial cells, but decreased survival of newly born neurons. These A beta-induced neurogenic effects were also observed in choroid plexus of APP/PS1 mice, and detected also in autopsy tissue from AD patients. Analysis of signaling pathways revealed that pre-treating the choroid plexus epithelial cells with specific inhibitors of TyrK or MAPK diminished A beta-induced neuronal proliferation. Taken together, our results support a role of A beta in proliferation and differentiation in the choroid plexus epithelial cells in Alzheimer's disease.