As early as 20 years ago, Amadoro et al. [54] reported that an intracellular 20–22 kDa NH2 truncated Tau fragment was largely enriched in the mitochondria of human AD brain synaptosomes and that the amount of Tau in the terminal fields correlated with both pathological synaptic changes and impairment functional organelles. This evidence concerns the gene MAPT and Alzheimer disease.