For example, dysfunctional synaptic activity has been shown to promote the spread of tau; in vitro and in vivo models of AD have demonstrated that increased neuronal activity stimulates tau release which further enhances tau pathology (Wu et al. [87], [88]) as well as spread of Aβ [73], consistent with preclinical human fMRI studies that have also shown pathology to be initiated in the LEC [33]. The gene discussed is MAPT; the disease is Alzheimer disease.