The presence of tau tangles is another well-known factor that is thought to contribute to the network alterations during AD, and interestingly, spontaneous epileptiform activity seen in many familial AD mouse models has been shown to be preceded by the presence of soluble endogenous tau, thus implicating tau as a crucial piece in the network impairment puzzle [39], [4], [44]. This evidence concerns the gene MAPT and Alzheimer disease.