MAPT and Alzheimer disease: In typical AD, tau accumulation is first observed in the entorhinal cortex (Braak stages I–II), followed sequentially by involvement of limbic and paralimbic structures (Braak stages III–IV) and association cortices (Braak stage V), and lastly primary cortices (i.e., primary sensorimotor, visual, or auditory cortices, Braak stage VI) (49,50).