PT  - JOURNAL ARTICLE
AU  - Wang, Baiping
AU  - Wang, Zilai
AU  - Sun, Lu
AU  - Yang, Li
AU  - Li, Hongmei
AU  - Cole, Allysa L.
AU  - Rodriguez-Rivera, Jennifer
AU  - Lu, Hui-Chen
AU  - Zheng, Hui
TI  - The Amyloid Precursor Protein Controls Adult Hippocampal Neurogenesis through GABAergic Interneurons
AID  - 10.1523/JNEUROSCI.2848-14.2014
DP  - 2014 Oct 01
TA  - The Journal of Neuroscience
PG  - 13314--13325
VI  - 34
IP  - 40
4099  - http://www.jneurosci.org/content/34/40/13314.short
4100  - http://www.jneurosci.org/content/34/40/13314.full
SO  - J. Neurosci.2014 Oct 01; 34
AB  - Impaired neurogenesis in the adult hippocampus has been implicated in AD pathogenesis. Here we reveal that the APP plays an important role in the neural progenitor proliferation and newborn neuron maturation in the mouse dentate gyrus. APP controls adult neurogenesis through a noncell-autonomous mechanism by GABAergic neurons, as selective deletion of GABAergic, but not glutamatergic, APP disrupts adult hippocampal neurogenesis. APP, highly expressed in the majority of GABAergic neurons in the dentate gyrus, enhances the inhibitory tone to granule cells. By regulating both tonic and phasic GABAergic inputs to dentate granule cells, APP maintains excitatory–inhibitory balance and preserves cognitive functions. Our studies uncover an indispensable role of APP in the GABAergic system for controlling adult hippocampal neurogenesis, and our findings indicate that APP dysfunction may contribute to impaired neurogenesis and cognitive decline associated with AD.