This may include amyloid angiopathy, decreased clearance of CNS ß-amyloid, tau-induced blood vessel abnormalities, and blood–brain barrier (BBB) impairment with disease progression.30,38,49,50 In this regard, the existing and/or exacerbated cholinergic deficit in aged AD mice limits the rCBF response reaching the highest rCBF response level (rCBFmax) to neuronal activity from the lower basal rCBF level, even though the % ΔrCBF to ACh in old AD mice was not significantly lower compared to it in aged WT mice (Fig. 2C and I). Here, MAPT is linked to Alzheimer disease.