Microtubule-associated protein (MAP) tau is abnormally hyperphosphorylated and aggregated into paired helical filaments (PHFs) or straight filaments (SFs) forming neurofibrillary tangles (NFTs) in the brains of patients with Alzheimer's disease (AD) and related tauopathies1, 2. Here, MAPT is linked to early-onset autosomal dominant Alzheimer disease.