Selective Degeneration of Entorhinal-CA1 Synapses in Alzheimer's Disease via Activation of DAPK1.

Excitatory pyramidal neurons in the entorhinal cortical layer II region (ECII_PN) form functional excitatory synapses with CA1 parvalbumin inhibitory neurons (CA1_PV) 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 ECII_PN of AD mice. Inhibition of DAPK1 by deleting a catalytic domain or a death domain of DAPK1 rescues the ECII_PN-CA1_PV synaptic loss and improves spatial learning and memory in AD mice. This study demonstrates that activation of DAPK1 in ECII_PN contributes to a memory loss in AD and hence warrants a promising target for the treatment of AD. [ABSTRACT FROM AUTHOR]