This is downregulated during decreased brain glucose metabolism directly related to functional insulin presence within the brain. This down-regulation leads to hyperphosphorylation of the tau protein [19]. Overall, impairment of insulin signaling is directly associated with tau phosphorylation. Interestingly, in postmortem AD and other tauopathies, insulin is accumulated as oligomers in the hyperphosphorylated tau-containing neurons [22]. The gene discussed is INS; the disease is Alzheimer disease.