Fig. 9

Schematic demonstration of a “vicious cycle” hypothesis. We believe that chronic cerebral hypoperfusion and aberrant generation of amyloid are the two key components forming the vicious cycles for vascular dysfunction and dementia. Compared to ischemia-induced severe hypoperfusion, eNOS-deficiency may result in milder but more chronic hypoperfusion, pointing to a novel pathophysiological mechanism in the vascular deficits of AD that ultimately leads to the aforementioned vicious cycles. SAD: sporadic Alzheimer’s disease; CBF: cerebral blood flow