Neuronal levels and sequence of tau modulate the power of brain rhythms.

Neuronal levels and sequence of tau modulate the power of brain rhythms. Neurobiol Dis. 2018 May 31;: Authors: Das M, Maeda S, Hu B, Yu GQ, Guo W, Lopez I, Yu X, Tai C, Wang X, Mucke L Abstract Neural network dysfunction may contribute to functional decline and disease progression in neurodegenerative disorders. Diverse lines of evidence suggest that neuronal accumulation of tau promotes network dysfunction and cognitive decline. The A152T-variant of human tau (hTau-A152T) increases the risk of Alzheimer's disease (AD) and several other tauopathies. When overexpressed in neurons of transgenic mice, it causes age-dependent neuronal loss and cognitive decline, as well as non-convulsive epileptic activity, which is also seen in patients with AD. Using intracranial EEG recordings with electrodes implanted over the parietal cortex, we demonstrate that hTau-A152T increases the power of brain oscillations in the 0.5-6 Hz range more than wildtype human tau in transgenic lines with comparable levels of human tau protein in brain, and that genetic ablation of endogenous tau in Mapt-/- mice decreases the power of these oscillations as compared to wildtype controls. Suppression of hTau-A152T production in doxycycline-regulatable transgenic mice reversed their abnormal network activity. Treatment of hTau-A152T mice with the antiepileptic drug levetiracetam also rapidly and persistently reversed their brain dysrhythmia and network hypersynchrony...
Source: Neurobiology of Disease - Category: Neurology Authors: Tags: Neurobiol Dis Source Type: research