MAPT and Alzheimer disease: In this review, we will briefly discuss four influential hypotheses for AD: the amyloid cascade hypothesis that has dominated the field for decades, the tau hypothesis that gained much more attention following repeated clinical failures using Aβ-centered targeting strategies, the pathogen hypothesis that has gained supporting evidence from recent publications, and the “antimicrobial protection hypothesis” that revisits the amyloid hypothesis in the context of microbial pathogen response.