MAPT and Alzheimer disease: Pathophysiological hallmarks are the accumulation and aggregation of extracellular amyloid-β (Aβ), intracellular neurofibrillary tangles composed of hyperphosphorylated tau, neuroinflammation, synaptic toxicity, and neuronal death.1,2,3 Dominantly inherited AD (DIAD) is caused by variants in APP, PSEN1, or PSEN2 genes, with carriers developing cognitive impairment at a predictable, young age.4