Pathological changes begin years before symptoms onset in AD and are characterized by an abnormal accumulation of extracellular aggregates of amyloid-β peptides leading to senile plaques and intracellular aggregates of hyperphosphorylated tau proteins leading to neurofibrillary tangles (see Refs.1, 2 for a description of the progressive cerebral deposition). Here, MAPT is linked to Alzheimer disease.