MAPT and Alzheimer disease: Tau pathology progresses through well-defined stereotyped stages, which appears to be initiated in the locus coeruleus and slowly spreads via the entorhinal cortex and hippocampus to the neocortex [12, 13]; however the role of the locus coeruleus is controversial [4]. This pattern of tau spreading led to the suggestion that AD progression occurs by neuron-to-neuron transmission involving trans-synaptic transport of seeds of tau aggregation from affected to anatomically interconnected recipient neurons [12, 13].