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 4-9 month-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-beta plaques affect their generation. The EEG of the APP/PS1 trans genic 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 (60 mg/kg; i.p.) was injected. Moreover, physostigmine injection (1 mg/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-beta plaques. Application of N-(2-chloroethyl)-N-ethyl-bromobenzylamine (50 mg/kg) generated amyloid-beta plaques in the cortex and seizure activity appeared. Taken together, these data indicate that deposits of amyloid-beta 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. (C) 2017 Published by Elsevier B.V.