Seizure susceptibility in the APP/PS1 mouse model of Alzheimer's disease and relationship with amyloid β plaques

Alzheimer's disease is a common age associated neurodegenerative disorder associated with an elevated risk of seizures that may be fundamentally connected to cognitive dysfunction. We used 4-9month-old mice of the APP/PS1 mouse model of Alzheimer's disease to study the presence of epileptiform-like discharges and to establish if the amyloid-β plaques affect their generation. The EEG of the APP/PS1 transgenic mice revealed a higher incidence of epileptiform-like discharges i.e. seizure events (interictal spikes, sharp waves, or polyspikes) than in the controls. Also, APP/PS1 mice showed a lower latency to evoke seizure events than in the control animals when pentylenetetrazole (60mg/kg; i.p.) was injected. Moreover, physostigmine injection (1mg/kg; i.p.) also increased the frequency of spontaneous epileptiform-like discharges in the APP/PS1 mice. We also found a correlation between the frequency of epileptiform-like discharges and the number of amyloid-β plaques. Application of N-(2-chloroethyl)-N-ethyl-bromobenzylamine (50mg/kg) generated amyloid-β plaques in the cortex and seizure activity appeared. Taken together, these data indicate that deposits of amyloid-β plaques may be responsible for the epileptiform-like discharges recorded in the APP/PS1 mice and could be responsible for the elevated risk for seizures of Alzheimer's patients.