Brivaracetam, but not ethosuximide, reverses memory impairments in an Alzheimer's disease mouse model
This study aimed at demonstrating the efficacy of two antiepileptic drugs (AEDs) brivaracetam and ethosuximide in treating impairments in spatial memory in two AD mouse models. Using continuous in vivo electroencephalography (EEG) recording, coupled with spatial memory testing, the authors studied whether epileptiform discharges in transgenic AD mice could be used as a marker of drug efficacy for memory improvement. The authors report that, in two transgenic mouse models of AD (APP/PS1 and 3xTg-AD), the presence of spike-wave discharges (SWDs) correlated with impairments in spatial memory,although a weaker correlation was seen in 3xTg-AD mice. Both ethosuximide and brivaracetam reduced mouse SWDs, but only brivaracetam reversed memory impairments in APP/PS1 mice. Biochemical and immunohistochemical analyses indicated that epileptiform discharges were not associated with changes in Aβ metabolism or deposition. Data showed that, similar to levetiracetam, brivaracetam interacts with synapticvesicle protein 2A (SV2A), and confirm that targeting SV2A, which results in broad-spectrum anticonvulsant action, reverses memory impairments in the APP/PS1 model of AD. Finally, while SWDs in APP/PS1 mice correlate with impairments in spatial memory, the reduction of these discharges is not a reliable surrogate marker of preclinical drug efficacy in the APP/PS1 AD mouse model.