Recommendations for Preclinical Testing of Treatments Against Alzheimer's Disease-Related Epileptiform Spikes in Transgenic Rodent Models

Abstract

Recent evidence suggests that about 30%of patients with mild to moderate Alzheimer's disease (AD) without a known diagnosis of epilepsy may display epileptiform spikes during electroencephalographic (EEG) recordings. These abnormal discharges occur predominantly during sleep and may be associated with accelerated disease progression. Subclinical spikes may represent a relevant target for clinical drug interventions, and there is a clear unmet need for preclinical testing of novel disease modifying agents in suitable animal models. Transgenic rodent models of AD pathology exhibit various forms of epileptiform EEG activity related to the abnormal levels of amyloid species in the brain. Among them, large-amplitude cortical and hippocampal EEG spikes in mouse and rat AD models may be reminiscent of the subclinical epileptiform EEG spikes recorded in some AD patients. This article reports the recommendations of a multidisciplinary panel of experts on optimal EEG markers and experimental designs to measure and report epileptiform activities and their response to symptomatic and disease-modifying drugs in transgenic AD model rodents. These recommendations may harmonize future preclinical EEG studies in the drug discovery research and may increase the comparability of experimental outcomes and their translational clinical value.