Increased phosphoglycerate kinase in the brains of patients with Down's syndrome but not with Alzheimer's disease

Impaired glucose metabolism in Down's syndrome (DS) has been well-documente d in vivo, although information on the underlying biochemical defect is lim ited and no biochemical studies on glucose handling enzymes have been carri ed out in the brain. Through gene hunting in fetal DS brain we found an ove rexpressed sequence homologous to the phosphoglycerate kinase (PGK) gene. T his finding was studied further by investigating the activity levels of thi s key enzyme of carbohydrate metabolism in the brains of patients with DS. PGK activity was determined in five brain regions of nine patients with DS, nine patients with Alzheimer's disease and 14 controls. PGK activity was s ignificantly elevated in the frontal, occipital and temporal lobe and in th e cerebellum of patients with DS. PGK activity in corresponding brain regio ns of patients with Alzheimer's disease was comparable with controls. We co nclude that our findings complement previously published data on impaired b rain glucose metabolism in DS evaluated by positron emission tomography in clinical studies. Furthermore, we show that in DS, impaired glucose metabol ism, represented by increased PGK activity, is a specific finding rather th an a secondary phenomenon simply due to neurodegeneration or atrophy. These observations are also supported by data from subtractive hybridization, sh owing overexpressed PGK in DS brains at the transcriptional level early in life.