The original amyloid cascade hypothesis stated that the extracellular deposition of insoluble beta-amyloid (Aβ) plaques drives intracellular tau phosphorylation, the formation of neurofibrillary tangles (NFTs), and the subsequent neurodegeneration which underlies the pathology of Alzheimer’s disease (AD) [26]. Here, MAPT is linked to early-onset autosomal dominant Alzheimer disease.