Increased glyceraldehyde 3-phosphate dehydrogenase levels in the brain of patients with Down's syndrome.

Impaired glucose metabolism in Down's syndrome (DS) has been well-documented in vivo, although information on the underlying biochemical defect is limited and no biochemical studies on glucose handling enzymes have been carried out in the brain. In a previous study, we found by gene hunting in DS brain an overexpressed sequence homologous to the glyceraldehyde 3-phosphate dehydrogenase (G3PD) gene. Here we studied G3PD activity and expression levels, using two-dimensional gel analysis, in five brain regions of patients with DS and Alzheimer's disease (AD). The protein expression levels in four brain areas were approximately 1.5-fold higher in patients with DS in comparison with the controls. G3PD activity was significantly elevated in the frontal, parietal, occipital and temporal lobe of DS as well, but not in the corresponding AD brain regions. We conclude that our biochemical findings complement previously published data of impaired brain glucose metabolism in DS evaluated by positron emission tomography in clinical studies.