Increased neuronal glucose-6-phosphate dehydrogenase and sulfhydryl levelsindicate reductive compensation to oxidative stress in Alzheimer disease

We analyzed glucose-6-phosphate dehydrogenase, the rate-controlling enzyme of the pentose phosphate pathway and free sulfhydryls, to study redox balan ce in Alzheimer disease, Glucose-6-phosphate dehydrogenase plays a pivotal role in homeostatic redox control by providing reducing equivalents to glut athione, the major nonenzymatic cellular antioxidant. There is a multitude of evidence that marks oxidative stress proximally in the natural history o f Alzheimer disease. Consistent with a role for glutathione in defense agai nst increased reactive oxygen, we found an upregulation of glucose-6-phosph ate dehydrogenase together with increased sulfhdryls in Alzheimer disease. These data indicate that reductive compensation may play an important role in combating oxidative stress in Alzheimer disease. (C) 1999 Academic Press .