Six tau isoforms with three microtubule-binding domain repeats (3R tau) or four microtubule-binding repeats (4R tau) are expressed in human brain and aggregated into tau pathologies in patients with Alzheimer’s disease.85 One of the limitations of this study using mouse models is that only three 4R tau isoforms are expressed in the mouse brain.51,86 Although the primary structures of human and mouse tau proteins are highly conserved, they differ in several amino acids, especially in their N-terminal regions. Here, MAPT is linked to early-onset autosomal dominant Alzheimer disease.