Reduced activities of thiamine-dependent enzymes in the brains and peripheral tissues of patients with Alzheimer's disease

Arch Neurol. 1988 Aug;45(8):836-40. doi: 10.1001/archneur.1988.00520320022009.


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.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Aged
  • Alzheimer Disease / enzymology*
  • Alzheimer Disease / pathology
  • Animals
  • Brain / enzymology*
  • Erythrocytes / enzymology
  • Female
  • Fibroblasts / enzymology
  • Humans
  • Ketoglutarate Dehydrogenase Complex / blood
  • Ketoglutarate Dehydrogenase Complex / metabolism*
  • Ketone Oxidoreductases / metabolism*
  • Male
  • Skin / enzymology*
  • Skin / pathology
  • Thiamine / physiology*
  • Thiamine Pyrophosphate / pharmacology
  • Transketolase / metabolism


  • Ketone Oxidoreductases
  • Ketoglutarate Dehydrogenase Complex
  • Transketolase
  • Thiamine Pyrophosphate
  • Thiamine