MAPT and early-onset autosomal dominant Alzheimer disease: A causal influence of blood flow changes on the cognitive changes at the onset of Alzheimer’s disease, before synapses or neurons are lost, is suggested by the fact that the reduction of cerebral blood flow starts early in preclinical AD [107, 180], with a faster onset than the deposition of Aβ or tau [76], and the fall of metabolism is also an early event [81, 115].