Conclusions
Our data confirm an intriguing therapeutic role of anticonvulsant drugs targeting synaptic vesicle protein 2A across AD mouse models. Chronic ethosuximide dosing did not reverse spatial memory impairments in APP/PS1 mice, despite reduction of SWDs. Our data indicate that SWDs are not a reliable surrogate marker of appropriate target engagement for reversal of memory dysfunction in APP/PS1 mice.
Methods
Transgenic AD mice (APP/PS1 and 3xTg-AD) were chronically implanted with dural electroencephalography electrodes, and epileptiform activity was correlated with spatial memory function and transgene-specific pathology. The antiepileptic drugs ethosuximide and brivaracetam were tested for their ability to suppress epileptiform activity and to reverse memory impairments and synapse loss in APP/PS1 mice.
Results
We 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. Both ethosuximide and brivaracetam reduce mouse SWDs, but only brivaracetam reverses memory impairments in APP/PS1 mice. Conclusions: Our data confirm an intriguing therapeutic role of anticonvulsant drugs targeting synaptic vesicle protein 2A across AD mouse models. Chronic ethosuximide dosing did not reverse spatial memory impairments in APP/PS1 mice, despite reduction of SWDs. Our data indicate that SWDs are not a reliable surrogate marker of appropriate target engagement for reversal of memory dysfunction in APP/PS1 mice.