MAPT and Alzheimer disease: According to this staging system, hyperphosphorylated Tau accumulates first in the entorhinal cortex and locus coeruleus before the disease becomes symptomatic; the propagation of Tau pathology beyond entorhinal cortex and locus coeruleus by neuron-to-neuron transmission is initiated after accumulation of a high β-amyloid load in isocortical regions and is associated with symptoms of AD, according to pathological, clinical, and biomarker data (4).