MAPT and Alzheimer disease: Interestingly, the accumulation of synaptic hyperphosphorylated and HMW tau correlates with the accumulation of synaptic ubiquitinated proteins in AD brains and mouse models (Tai et al., 2012; Schaler et al., 2021), suggesting a disruption of synaptic proteasome-mediated proteolysis, which can further lead to synaptic damage and synaptic loss.