Affected enzyme activities in Alzheimer's disease are sensitive to antemortem hypoxia

Many enzyme activities in Alzheimer's disease (AD) are changed. Some of these enzyme activities are related to certain neurotransmitter systems. Enzymes in the brain can also be sensitive to antemortem hypoxia. In the present study it was determined if enzyme activities that are altered in AD are also subject to alteration by antemortem hypoxia. As an indicator of antemortem hypoxia brain lactate concentration was used. Enzyme activities measured were those of prolyl endopeptidase (PE), aminopeptidase (AP), phosphatidylinositol (PI) kinase, phosphatidylinositol phosphate kinase, alpha-ketoglutarate dehydrogenase (alpha-KGDH), choline acetyltransferase and beta-glucuronidase. All of these enzyme activities have been measured in AD patients before and several of them have been found to be decreased. In accordance with previous findings, PE, alpha-KGDH and ChAT activities were reduced in AD patients. PI kinase and beta-glucuronidase activities, however, were not reduced, contrary to previous findings. All enzyme activities, except that of beta-glucuronidase, correlated with brain lactate concentration, suggesting that antemortem hypoxia has a major influence on the activity of enzymes in the brain. PE, AP, alpha-KGDH and ChAT activities were still different between AD and control samples when these were matched for lactate concentration. The enzyme activities that were changed in AD were also significantly correlated with lactate concentration, an indicator of antemortem hypoxia, in brain specimens. This suggests that antemortem hypoxia and AD have some factor in common that may be responsible for changes in enzyme activities. Since both PE and alpha-KGDH are known to be sensitive to oxidative stress this factor could be oxidative stress.