Data collected in a longitudinal study showed that the impairment of BVR-A is one of the earliest events observed during the development of brain insulin resistance in 3xTg-AD mice (a model to study AD) and that this phenomenon occurs before a consistent accumulation of Aβ and Tau pathology (well-known AD markers [83]) as well as increased TNFa levels (a main inducer of insulin resistance [79,80]) in the brain [81] (Table 2). This evidence concerns the gene MAPT and Alzheimer disease.