Pharmacological neuromodulation of on-going "Delta" and "Alpha" EEG rhythms: Evidence for translational neurophysiological biomarkers in Alzheimer's disease animal models. Issue 3 (March 2016) - Drinkenburg, W.H.
Abstract : Alzheimer's disease (AD) patients exhibit abnormalities in EEG delta and alpha rhythms, which correlate with disease progression and cognitive deterioration. Combined analysis of such abnormalities, with the alterations in neuronal network activity and underlying synaptic plasticity offers new preclinical tools with a potential for clinical use: in addition to translational readouts such as evoked potentials, sleep, and spectral EEG changes, we assessed neurophysiological indices of functional brain dynamics such as partial directed coherence, phase-amplitude and cross-frequency-coupling. These neurophysiological read-outs were evaluated in mouse models for AD, e.g. TASTPM, P301L Tau seeding or TS65dn model. Advanced analysis of cortical EEG and sleep was performed in aging transgenic mice, which develop amyloid plaques/hyperphosphorylated tau throughout the cortex and hippocampus and after pharmacological neuromodulation. Results support the hypothesis that amyloid plaque deposition and hyperphosphorylated tau elicits consistent, though differential neurophysiological changes, mediated via altered neuronal connectivity. Alterations are reflected by a shift away from delta frequency power during slow wave sleep (TASTPM; APP/PS1), or changes in gamma and theta oscillations and related cross frequency couplings (P301L Tau seeding; TS65dn), linked to disturbances in cognitive performance. Follow-up studies will validate those biomarkers that are most indicative for (early) disease intervention or symptomatic treatment.