The intracellular domain of amyloid precursor protein induces neuron-specific apoptosis

Although amyloid precursor protein (APP) has central roles in Alzheimer's disease, the physiological functions of this protein have yet to be fully elucidated. APP homologues show significant sequence conservation in the intracellular domain through evolution, which may reflect the functional importance of the intracellular domain of APP (AICD). To examine this possibility, we established embryonic carcinoma P19 cell lines overexpressing AICD. Although neurons could be differentiated from these cell lines with retinoic acid treatment, overexpression of AICD gave rise to neuron-specific cell death. Furthermore, DNA fragmentation was detected and TUNEL-positive cells were also Tuj1-positive neurons. Taken together, we concluded that AICD can induce neuron-specific apoptosis.