In 1991, the work of Braak proposed the sequence of progression of Alzheimer’s disease neuropathology, demonstrating that soluble hyperphosphorylated tau first appears in the locus coeruleus (LC) neurons and subsequently appears along LC axons to their terminals in the entorhinal cortex (EC) [49,50]. This evidence concerns the gene MAPT and early-onset autosomal dominant Alzheimer disease.