MAPT and Alzheimer disease: According to this staging system, the initial accumulation of hyperphosphorylated tau occurs before the disease becomes symptomatic; the propagation of tau pathology beyond the entorhinal cortex and locus coeruleus by neuron-to-neuron transmission is initiated after accumulation of a high Aβ load in iso-cortical regions and is associated with symptoms of AD, according to pathological, clinical and biomarker data6.