Impaired brain glucose metabolism in patients with Down syndrome.
A series of impaired metabolic functions in Down Syndrome (DS) including glucose handling has been described. Recent information from positron emission tomography studies in DS patients and our finding of downregulated phosphoglucose isomerase (PGI) in fetal brain with DS by gene hunting using subtractive hybridization, made us investigate PGI, a key enzyme of glucose metabolism, in brain of patients with DS, Alzheimer's disease (AD) and controls. PGI and phosphofructokinase (PFK) activities were determined in frontal, parietal, temporal, occipital lobe and cerebellum of 9 controls, 9 patients with DS and 9 patients with AD. PGI activity in DS brain was significantly decreased in frontal, temporal lobe and cerebellum, comparable to controls in parietal lobe and elevated in occipital lobe. Brain PGI activity of patients with AD was comparable to controls in all regions tested, PFK, a rate limiting enzyme of glucose metabolism, was comparable between all brain regions of all three groups. Data of this study confirm impaired glucose metabolism in DS proposed in literature and found by positron emission tomography (PET) studies. We show that changes in glucose handling in patients with AD as evaluated by PET studies are not supported by our data, although not contradictory, as determinants other than glucose metabolizing enzymes as e.g. vascular factors and glucose transport may account for these findings. Changes of downregulated PGI found by subtractive hybridization at the transcriptional level in fetal DS brain along with our findings in DS brain regions suggest a strong specific link between glucose metabolism and DS rather than AD.
Labudova
O
O
Department of Pediatrics, University of Vienna, Austria.
Cairns
N
N
Kitzmüller
E
E
Lubec
G
G
D000368:Aged; D000544:Alzheimer Disease / Q000378:metabolism*; D000595:Amino Acid Sequence; D001483:Base Sequence; D001921:Brain / Q000196:embryology / Q000378:metabolism*; D004314:Down Syndrome / Q000196:embryology / Q000235:genetics* / Q000378:metabolism*; D005260:Female; D005333:Fetus; D005956:Glucose-6-Phosphate Isomerase / Q000235:genetics / Q000378:metabolism; D006624:Hippocampus / Q000196:embryology / Q000378:metabolism; D006801:Humans; D008297:Male; D008875:Middle Aged; D008969:Molecular Sequence Data; D010732:Phosphofructokinase-1 / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics; D016415:Sequence Alignment; D012689:Sequence Homology, Nucleic Acid
D012333:RNA, Messenger; D010732:Phosphofructokinase-1; D005956:Glucose-6-Phosphate Isomerase