Soluble APP functions as a vascular niche signal that controls adult neural stem cell number

Abstract

The molecular mechanism by which NSC number is controlled in the neurogenic regions of the adult brain is not fully understood but it has been shown that vascular niche signals regulate neural stem cell (NSC) quiescence and growth. Here, we have uncovered a role for soluble amyloid precursor protein (sAPP) as a vascular niche signal in the subventricular zone (SVZ) of the lateral ventricle of the adult mouse brain. sAPP suppresses NSC growth in culture. Further in vivo studies on the role of APP in regulating NSC number in the SVZ clearly demonstrate that endothelial deletion of App causes a significant increase in the number of BrdU label-retaining NSCs in the SVZ, whereas NSC/astrocyte deletion of App has no detectable effect on the NSC number. Taken together, these results suggest that endothelial APP functions as a vascular niche signal that negatively regulates NSC growth to control the NSC number in the SVZ.