PT - JOURNAL ARTICLE AU - Shu Shu AU - Houze Zhu AU - Na Tang AU - Wenting Chen AU - Xinyan Li AU - Hao Li AU - Lei Pei AU - Dan Liu AU - Yangling Mu AU - Qing Tian AU - Ling-Qiang Zhu AU - Youming Lu TI - Selective Degeneration of Entorhinal-CA1 Synapses in Alzheimer's Disease via Activation of DAPK1 AID - 10.1523/JNEUROSCI.2258-16.2016 DP - 2016 Oct 19 TA - The Journal of Neuroscience PG - 10843--10852 VI - 36 IP - 42 4099 - http://www.jneurosci.org/content/36/42/10843.short 4100 - http://www.jneurosci.org/content/36/42/10843.full SO - J. Neurosci.2016 Oct 19; 36 AB - Excitatory pyramidal neurons in the entorhinal cortical layer II region (ECIIPN) form functional excitatory synapses with CA1 parvalbumin inhibitory neurons (CA1PV) and undergo selective degeneration in the early stages of Alzheimer's disease (AD). Here, we show that death-associated protein kinase 1 (DAPK1) is selectively activated in ECIIPN of AD mice. Inhibition of DAPK1 by deleting a catalytic domain or a death domain of DAPK1 rescues the ECIIPN-CA1PV synaptic loss and improves spatial learning and memory in AD mice. This study demonstrates that activation of DAPK1 in ECIIPN contributes to a memory loss in AD and hence warrants a promising target for the treatment of AD.SIGNIFICANCE STATEMENT Our recent study reported that excitatory pyramidal neurons in the entorhinal cortical layer II region (ECIIPN) target to CA1 parvalbumin-type inhibitory neurons (CA1PV) at a direct pathway and are one of the most vulnerable brain cells that are selectively degenerated in the early stage of Alzheimer's disease (AD). Our present study shows that death-associated protein kinase 1 (DAPK1) is selectively activated in ECIIPN of AD mice. Inhibition of DAPK1 by deleting a catalytic domain or a death domain of DAPK1 rescues the ECIIPN-CA1PV synaptic loss and improves spatial learning and memory in the early stage of AD. These data not only demonstrate a crucial molecular event for synaptic degeneration but also provide a therapeutic target for the treatment of AD.