Likewise, neurofibrillary tangles, composed of intracellular deposits of tau protein, and extracellular beta-amyloid plaques can occur before the onset of cognitive symptoms and have been shown to promote glucose hypometabolism in AD (Beason-Held et al., 2013; Bischof et al., 2016; Ingelsson et al., 2004). This evidence concerns the gene MAPT and Alzheimer disease.