As described in patients, and elucidated in animal models, this 4R tauopathy manifests the following indications in the brain throughout the pathological progress: a synaptic loss, followed by hyperphosphorylation of the tau protein, leading to neurofibrillary degeneration, ultimately resulting in neuronal loss (Spillantini et al., 1998; Yoshiyama et al., 2007). The gene discussed is MAPT; the disease is tauopathy.