MAPT and Alzheimer disease: Alzheimer’s disease (AD) is characterized by the accumulation of two proteins in the brain that pre-date the clinical onset of symptoms by several decades1–5: extracellular Aβ-amyloid (Aβ) plaques that initiate in the neocortex and gradually spread through the brain, and intracellular tau neurofibrillary tangles, which are most evident in the entorhinal cortex and the limbic system6–8.