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. Through gene hunting in fetal DS brain we found an overexpressed sequence homologous to the phosphoglycerate kinase (PGK) gene. This finding was studied further by investigating the activity levels of this 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 significantly elevated in the frontal, occipital and temporal lobe and in the cerebellum of patients with DS. PGK activity in corresponding brain regions of patients with Alzheimer's disease was comparable with controls. We conclude that our findings complement previously published data on impaired brain glucose metabolism in DS evaluated by positron emission tomography in clinical studies. Furthermore, we show that in DS, impaired glucose metabolism, represented by increased PGK activity, is a specific finding rather than a secondary phenomenon simply due to neurodegeneration or atrophy. These observations are also supported by data from subtractive hybridization, showing overexpressed PGK in DS brains at the transcriptional level early in life.
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March 01 1999
Increased phosphoglycerate kinase in the brains of patients with Down's syndrome but not with Alzheimer's disease
Olga LABUDOVA;
Olga LABUDOVA
1Department of Pediatrics, University of Vienna, Waehringer Guertel 18, A 1090 Vienna, Austria
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Erwin KITZMUELLER;
Erwin KITZMUELLER
1Department of Pediatrics, University of Vienna, Waehringer Guertel 18, A 1090 Vienna, Austria
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Hermann RINK;
Hermann RINK
*Department of Radiobiology, University of Bonn, Sigmund Freud Strasse 25, D-53105 Bonn, Germany, and
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Nigel CAIRNS;
Nigel CAIRNS
†Institute of Psychiatry, Department of Neuropathology, Brain Bank, De Crispigny Park, Denmark Hill, London SE5 8AF, U.K.
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Gert LUBEC
1Department of Pediatrics, University of Vienna, Waehringer Guertel 18, A 1090 Vienna, Austria
Correspondence: Professor G. Lubec.
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Publisher: Portland Press Ltd
Received:
April 28 1998
Revision Received:
July 02 1998
Accepted:
October 14 1998
Online ISSN: 1470-8736
Print ISSN: 0143-5221
The Biochemical Society and the Medical Research Society © 1999
1999
Clin Sci (Lond) (1999) 96 (3): 279–285.
Article history
Received:
April 28 1998
Revision Received:
July 02 1998
Accepted:
October 14 1998
Citation
Olga LABUDOVA, Erwin KITZMUELLER, Hermann RINK, Nigel CAIRNS, Gert LUBEC; Increased phosphoglycerate kinase in the brains of patients with Down's syndrome but not with Alzheimer's disease. Clin Sci (Lond) 1 March 1999; 96 (3): 279–285. doi: https://doi.org/10.1042/cs0960279
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