Reduced activities of thiamine-dependent enzymes in the brains and peripheral tissues of patients with Alzheimer's disease.
A report of cell loss in the nucleus basalis of Meynert in patients with Wernicke-Korsakoff disease prompted the examination of thiamine pyrophosphate (TPP)-dependent enzymes in the brain and peripheral tissues of patients with Alzheimer's disease. In these brains, the activities of the 2-ketoglutarate dehydrogenase complex were reduced more than 75% and those of transketolase more than 45%. Decreases occurred in histologically damaged and in relatively undamaged areas. Small but statistically significant abnormalities of transketolase, but not of 2-ketoglutarate dehydrogenase complex, were identified in red blood cells and cultured fibroblasts. Previous studies have shown deficiencies in the brain and variable effects in peripheral tissues on another TPP-dependent enzyme--the pyruvate dehydrogenase complex. Activities of TPP-dependent enzymes appear to be deficient in the brain and perhaps in some peripheral tissues in patients with Alzheimer's disease.
Gibson
G E
GE
Department of Neurology, Cornell University Medical College, White Plains, NY 10605.
Sheu
K F
KF
Blass
J P
JP
Baker
A
A
Carlson
K C
KC
Harding
B
B
Perrino
P
P
D000368:Aged; D000544:Alzheimer Disease / Q000201:enzymology* / Q000473:pathology; D000818:Animals; D001921:Brain / Q000201:enzymology*; D004912:Erythrocytes / Q000201:enzymology; D005260:Female; D005347:Fibroblasts / Q000201:enzymology; D006801:Humans; D007655:Ketoglutarate Dehydrogenase Complex / Q000097:blood / Q000378:metabolism*; D007658:Ketone Oxidoreductases / Q000378:metabolism*; D008297:Male; D012867:Skin / Q000201:enzymology* / Q000473:pathology; D013831:Thiamine / Q000502:physiology*; D013835:Thiamine Pyrophosphate / Q000494:pharmacology; D014174:Transketolase / Q000378:metabolism
D007658:Ketone Oxidoreductases; D007655:Ketoglutarate Dehydrogenase Complex; D014174:Transketolase; D013835:Thiamine Pyrophosphate; D013831:Thiamine