Background::Insufficient cerebral perfusion is suggested to play a role in the development of Alzheimer disease (AD). However, there is a lack of direct evidence indicating whether hypoperfusion causes or aggravates AD pathology. We investigated the effect of chronic cerebral hypoperfusion on AD-related pathology in humans.Methods::We enrolled a group of cognitively normal patients (median age: 64 years) with unilateral chronic cerebral hypoperfusion. Regions of interest with the most pronounced hypoperfusion changes were chosen in the hypoperfused region and were then mirrored in the contralateral hemisphere to create a control region with normal perfusion. n 11C-Pittsburgh compound-positron emission tomography standard uptake ratios and brain atrophy indices were calculated from the computed tomography images of each patient.n Results::The median age of the 10 participants, consisting of 4 males and 6 females, was 64 years (47-76 years). We found that there were no differences in standard uptake ratios of the cortex (volume of interest [VOI]: n P = 0.721, region of interest [ROI]: n P = 0.241) and grey/white ratio (VOI: n P = 0.333, ROI: n P = 0.445) and brain atrophy indices (Bicaudate, Bifrontal, Evans, Cella, Cella media, and Ventricular index, n P > 0.05) between the hypoperfused regions and contralateral normally perfused regions in patients with unilateral chronic cerebral hypoperfusion.n Conclusion::Our findings suggest that chronic hypoperfusion due to large vessel stenosis may not directly induce cerebral β-amyloid deposition and neurodegeneration in humans.“,”Background::Insufficient cerebral perfusion is suggested to play a role in the development of Alzheimer disease (AD). However, there is a lack of direct evidence indicating whether hypoperfusion causes or aggravates AD pathology. We investigated the effect of chronic cerebral hypoperfusion on AD-related pathology in humans.Methods::We enrolled a group of cognitively normal patients (median age: 64 years) with unilateral chronic cerebral hypoperfusion. Regions of interest with the most pronounced hypoperfusion changes were chosen in the hypoperfused region and were then mirrored in the contralateral hemisphere to create a control region with normal perfusion. n 11C-Pittsburgh compound-positron emission tomography standard uptake ratios and brain atrophy indices were calculated from the computed tomography images of each patient.n Results::The median age of the 10 participants, consisting of 4 males and 6 females, was 64 years (47-76 years). We found that there were no differences in standard uptake ratios of the cortex (volume of interest [VOI]: n P = 0.721, region of interest [ROI]: n P = 0.241) and grey/white ratio (VOI: n P = 0.333, ROI: n P = 0.445) and brain atrophy indices (Bicaudate, Bifrontal, Evans, Cella, Cella media, and Ventricular index, n P > 0.05) between the hypoperfused regions and contralateral normally perfused regions in patients with unilateral chronic cerebral hypoperfusion.n Conclusion::Our findings suggest that chronic hypoperfusion due to large vessel stenosis may not directly induce cerebral β-amyloid deposition and neurodegeneration in humans.