While the association between increased oxidative stress andincreasing bioenergetic dysfunction, as evidenced by increasing glucosehypometabolism, increased lactate and pyruvate and the development of increasingsynaptic dysfunction seen in preclinical AD and APOE ε4 carriers, is not associated with Aβ accumulation [257] (reviewed by [258]), recent research suggests that this mightnot be the case for tau deposition although findings are mixed [259–261]. Here, MAPT is linked to Alzheimer disease.