In the htau mouse model classical AD histopathology is well established by 12-months of age, where the distribution of tau is similar to that observed in human brains (Polydoro et al., 2009); however, unlike in humans it is not yet clear if synaptic accumulation of pathological tau precedes cognitive impairment (Polydoro et al., 2009; Cho et al., 2021). Here, MAPT is linked to Alzheimer disease.