The suppression of brain-wide perivascular transport may be, in part, attributed to the aging- or diabetes-dependent alterations in the cerebral vascular system, including the decline in vascular pulsatility [42,61], increase in vessel stiffness [8,62], loss of perivascular AQP4 polarization [24,42,63], abnormalities in perivascular space [24,64,65], decrease in microvascular density [66,67] and neurovascular uncoupling [68,69]. This evidence concerns the gene AQP4 and diabetes mellitus.