Increased homocysteine and decreased adenosine formation in Alzheimer's disease.

Vascular risk factors increase the risk of Alzheimer's disease. Increased concentrations of circulating homocysteine are associated with vascular risk factors and Alzheimer's disease but the underlying mechanisms are unclear. Homocysteine inhibits the hydrolysis of S-adenosylhomocysteine leading to a decrease in the intracellular adenosine concentration. Adenosine is an endogenous protective molecule against atherosclerotic and vaso-occlusive disorders that contribute to the pathology of Alzheimer's disease. In this study the concentrations of homocysteine and adenosine were determined in the plasma of 25 patients with Alzheimer's disease and 25 control subjects. There was a significant increase in the plasma concentration of homocysteine (p < 0.0001) and a significant decrease in the plasma concentration of adenosine (p < 0.001). In the combined Alzheimer and control groups a significant negative correlation was found between the plasma concentrations of homocysteine and adenosine (r = -0.769, p < 0.0001). There was also a significant negative correlation between the plasma concentrations of homocysteine and adenosine in the Alzheimer group (r =-0.773, p < 0.0001). The decrease in adenosine formation may play a role in the vascular pathology of homocysteine in Alzheimer's disease.