TY - JOUR T1 - The Amyloid Precursor Protein Controls Adult Hippocampal Neurogenesis through GABAergic Interneurons JF - The Journal of Neuroscience JO - J. Neurosci. SP - 13314 LP - 13325 DO - 10.1523/JNEUROSCI.2848-14.2014 VL - 34 IS - 40 AU - Baiping Wang AU - Zilai Wang AU - Lu Sun AU - Li Yang AU - Hongmei Li AU - Allysa L. Cole AU - Jennifer Rodriguez-Rivera AU - Hui-Chen Lu AU - Hui Zheng Y1 - 2014/10/01 UR - http://www.jneurosci.org/content/34/40/13314.abstract N2 - 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. ER -