Changes of activity and isozyme pattern of phosphofructokinase in the brains of patients with Alzheimer's disease.
A severe reduction of the in vivo cerebral glucose consumption rate is generally found in patients with Alzheimer's disease. In postmortem studies changes in the activities of key regulatory glycolytic enzymes, including 6-phosphofructokinase (PFK), have been reported in Alzheimer's disease brains, but the results obtained so far are inconsistent and controversial. We reevaluated the activity of PFK in brain tissue from clinically and neuropathologically confirmed cases of Alzheimer's disease using optimized tissue disintegration and assay methods and determined the PFK isozyme pattern. PFK activity in brains from patients with Alzheimer's disease was significantly increased in frontal and temporal cortex and unchanged in the other brain areas studied when compared with control brains. All three PFK isozymes were detected in each of the brain areas studied. In brains of Alzheimer's disease patients the level of the C-type PFK was slightly reduced at the expense of the M- and L-type subunits. The data presented do not support the results of other groups, which reported up to a 90% reduction of PFK activity in Alzheimer's disease. In contrast, the data presented clearly rule out the suggestion that changes of PFK activity might be one of the causes for the reduced glucose consumption in Alzheimer's disease brains.
Bigl
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Institute of Biochemistry, School of Medicine, University of Leipzig, Germany.
Bleyl
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Zedlick
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Arendt
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Bigl
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Eschrich
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K
D000368:Aged; D000369:Aged, 80 and over; D000544:Alzheimer Disease / Q000201:enzymology*; D000918:Antibody Specificity; D015153:Blotting, Western; D001921:Brain / Q000201:enzymology*; D002795:Choline O-Acetyltransferase / Q000378:metabolism; D003720:Densitometry; D004591:Electrophoresis, Polyacrylamide Gel; D005260:Female; D005634:Fructose-Bisphosphate Aldolase / Q000378:metabolism; D006801:Humans; D007527:Isoenzymes / Q000276:immunology / Q000378:metabolism*; D008297:Male; D010732:Phosphofructokinase-1 / Q000737:chemistry / Q000276:immunology / Q000378:metabolism*; D016622:Silver Staining
D007527:Isoenzymes; D002795:Choline O-Acetyltransferase; D010732:Phosphofructokinase-1; D005634:Fructose-Bisphosphate Aldolase