It was hypothesized that accumulation of toxic intracellular aggregate accompanied by a loss of soluble tau capable of stabilizing microtubules might synergistically lead to compromised neuronal survival (Lee et al., 2011), accounting for the putative relationship between NFT burden and cognitive decline in AD patients (Terry et al., 1981; Gomez-Isla et al., 1997). This evidence concerns the gene MAPT and Alzheimer disease.