There are two mainstream hypotheses for the pathogenesis of Alzheimer’s Disease: 1) the amyloid-β hypothesis posits amyloid-β accumulation initiates and drives tau pathology, causing neurodegeneration (Hardy and Selkoe, 2002); versus 2) the tau hypothesis postulates tau phosphorylation and aggregation initiates neurodegeneration (Arnsten et al., 2021). Here, MAPT is linked to early-onset autosomal dominant Alzheimer disease.