MAPT and early-onset autosomal dominant Alzheimer disease: Due to the complexity of the disease, understanding Alzheimer's disease (AD) pathophysiology well enough to find effective, meaningful treatments has only recently witnessed therapeutic breakthroughs with certain amyloid targeting, disease modifying monoclonal antibodies (mAbs).1, 2, 3 These results have provided insights into the cascade hypothesis that begins with amyloid beta (Aβ) accumulation, followed by Tau aggregation, spreading and ultimately neurodegeneration and cognitive impairment.4, 5, 6, 7 Diagnostic criteria and staging of AD have been recently updated.8