These studies show that while aging-related accumulation of tau, also known as primary age-related tauopathy, is mostly restricted to the entorhinal cortex, spread of tau beyond entorhinal cortex and into the adjacent parahippocampal regions only happens in the presence of Aβ indicating AD neuropathological changes.35-37 In this context, altered hyperexcitability in AD patients in the parahippocampus but not in the entorhinal cortex compared to healthy aging pose the question whether neuronal hyperexcitability play a role in the progression of AD-tauopathy beyond entorhinal regions. This evidence concerns the gene MAPT and Alzheimer disease.