Increased cortical beta power and spike-wave discharges in middle-aged APP/PS1 mice

Amyloid plaque-forming transgenic mice display neuronal hyperexcitability, epilepsy, and sudden deaths in early adulthood. However, it is unknown whether hyperexcitability persists until middle ages when memory impairment manifests. We recorded multichannel video electroencephalography (EEG), local field potentials, and auditory evoked potentials in transgenic mice carrying mutated human amyloid precursor protein (APP) and presenilin-1 (PS1) genes and wild-type littermates at 14-16 months and compared the results with data we have earlier collected from 4-month-old mice. Furthermore, we monitored acoustic startle responses in other APP/PS1 and wild-type mice from 3 to 11 months of age. Independent of the age APP/PS1 mice demonstrated increased cortical power at 8-60 Hz. They also displayed over 5-fold increase in the occurrence of spike-wave discharges and augmented auditory evoked potentials compared with nontransgenic littermates. In contrast to evoked potentials, APP/PS1 mice showed normalization of acoustic startle responses with aging. Increased cortical power and spike-wave discharges provide powerful new biomarkers to monitor progression of amyloid pathology in preclinical intervention studies.