Abnormal neuronal networks and seizure susceptibility in mice overexpressing the APP intracellular domain

Alterations in the processing of the amyloid precursor protein (APP) lead to familial Alzheimer's disease (AD). AD patients exhibit increased seizure susceptibility and alterations in their EEGs, which suggests that APP and its metabolites may modulate neuronal networks. Here we demonstrate that transgenic mice overexpressing APP intracellular domain (AICD) and its binding partner Fe65 exhibit abnormal spiking events and a susceptibility to induced seizures. These abnormalities are not observed in PDAPP(D664A) mice, which express high Aβ levels but harbor a mutation in the APP intracellular domain. These data suggest that alterations in the levels of AICD contribute to network dysfunction in AD.