Microvessels isolated from temporal cortex of patients with Alzheimer's disease showed decreased uptake of glucose when compared with vessels from age-matched or young control subjects. This was due to decreased hexokinase activity in the Alzheimer samples, as determined by ion exchange chromatography. This finding was confirmed independently by determination of the phosphorylation constant for hexokinase, K3, using positron emission tomography. The results suggest that Alzheimer's disease may result from a global defect in brain energy metabolism.