Epilepsy Drugs May Help Patients with Alzheimer’s Disease

Some epilepsy drugs may help to reverse memory loss in those with dementia. A recent study conducted by scientists from Yale University (New Haven, CT) and University of British Columbia (Vancouver, Canada) has found that targeting synaptic vesicle protein 2A in two transgenic Alzheimer’s disease (AD) mouse models (APP/PS1 and 3xTg-AD) can have a therapeutic effect on memory impairment.

Using the well-established link between familial AD and epileptic episodes, the researchers hypothesized that amyloid-beta (AB), the peptide derived from amyloid precursor protein (APP) that is widely believed to play a role in AD pathogenesis, may trigger the seizures and hyperactivity that ultimately worsen neuronal dysfunction in AD.

The researchers tested the effectiveness of the antiepileptic drugs brivaracetam, ethosuximide, and phenytoin—which target synaptic vesicle protein 2A—for reducing epileptic discharges and improving cognitive impairment in the APP model. Spike wave discharges (SWDs), which correlate with spatial memory impairment, were monitored using in vivo electroencephalography recordings. The results were consistent with the researchers’ hypothesis: AD mice overexpressing APP experienced epileptiform activity that correlated with SWDs. Likewise, there was a correlation between SWDs and impairments in the spatial memory, as the presence of SWDs worsened performance on memory tests.

Of the antiepileptic drugs, only ethosuximide and brivaracetam significantly reduced SWD levels in transgenic AD mice, whereas phenytoin had no effect. Only chronic treatment with brivaracetam succeeded in reversing the effects of memory impairment in the APP transgenic model, suggesting that a drug’s ability to reduce SWDs is not a reliable predictor of its ability to reverse memory dysfunction. Still, the success of brivaracetam and the experiment itself sheds light on the relationship between two prevalent neurological disorders and will no doubt have a profound impact on future research (https://alzres.com/content/7/1/25). — Sean McGuire