Previous research suggested that disruption of neuronal network activity may be a pathogenic factor early in the development of Alzheimer's disease. Now, Lennart Mucke and colleagues report that the antiepileptic drug levetiracetam (LEV) reverses synaptic dysfunction and learning problems in the human amyloid precursor protein (hAPP) transgenic mouse model of Alzheimer's disease (Proc. Natl. Acad. Sci. USA, published online 6 August 2012; doi:10.1073/pnas.1121081109). hAPP mice have abnormally high amounts of human amyloid-β and display abnormal neuronal network activity and epileptic seizures. Using video electroencephalography (EEG), the authors tested the efficacy of seven FDA-approved antiepileptic drugs in reducing abnormal spiking behavior. LEV had strong antiepileptic effects, so the authors then tested the effect of chronic treatment with LEV. These mice also showed reduction of epileptiform discharges. hAPP mice are hyperactive and spend more time than control mice in the open arms of the elevated plus maze, but chronic treatment with LEV reversed this behavior. To test whether treatment with LEV improves cognitive dysfunction in hAPP mice, learning and memory were tested by habituation to a novel environment and the Morris water maze. The authors found that chronic treatment with LEV improved learning and memory in these assays.
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