Soluble APP functions as a vascular niche signal that controls adult neural stem cell number [RESEARCH REPORT]

Yuya Sato, Yutaka Uchida, Jingqiong Hu, Tracy L. Young-Pearse, Takako Niikura, and Yoh-suke Mukouyama

What controls neural stem cell (NSC) number in the neurogenic regions of the adult brain? Vascular niche signals regulate 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 brain. sAPP suppresses NSC growth in culture. Further in vivo studies on the role of APP for the 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, while 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.

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