Translating network activity in an Alzheimer mouse model to human Alzheimer's disease mutation carriers

Abstract

BackgroundAlzheimer’s disease (AD) mouse models allow for the identification of cellular and molecular processes underlying neuronal network imbalance. In order to interpret these processes in a disease context, we need to link network changes in AD animals to those in human patients. Brain oscillations reflect neuronal network (im)balance and offer a tool to translate findings from mice to men. In this preliminary study, we investigate and compare cortical and hippocampal oscillatory activity using magnetoencephalography (MEG) in human patients and longitudinal electrophysiology recordings in AD mice.MethodsSource reconstructed resting state whole‐brain MEG of ten APP and PSEN1 mutation carriers and ten age‐ and gender‐matched control subjects were acquired. Carriers did not show objectively impaired cognitive functioning on any of the composite scores after extensive neuropsychological testing. Longitudinal local field potential recordings were obtained by implanted electrodes in APP/PS1 transgenic and wildtype controls from 3 until 10 months of age in different brain regions of the left hemisphere: hippocampus, prefrontal and parietal cortex. MEG analyses were constrained to similar brain regions. We estimated peak frequency, total (absolute broadband) and relative power across canonical frequency bands and compared these between human or mice mutation carriers and controls.ResultsHuman APP and PSEN1 mutation carriers showed lower peak frequency in the hippocampus and lower relative alpha 2 power in the precuneus and frontal cortex compared to controls (Fig1.). APP/PS1 mice also showed specific network alterations compared to wildtype control mice, but these seem to have more faster oscillations instead.ConclusionIn cognitively unimpaired human APP and PS1 mutation carriers we find oscillatory activity changes in the cortex and hippocampus, indicating network imbalance. However, opposite network changes are observed in the APP/PS1 AD mouse model compared to human mutation carriers using spectral measures. Future studies should explore other measures of network imbalance to identify potential cross‐species mechanistic links of early stage AD.