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Alterations of thiamine phosphorylation and of thiamine-dependent enzymes in Alzheimer's disease

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Abstract

There is a growing body of evidence to suggest that thiamine neurochemistry is disrupted in Alzheimer's Disease (AD). Studies in autopsied brain tissue from neuropathologically proven AD patients reveal significantly reduced activities of the thiamine phosphate dephosphorylating enzymes thiamine diphosphatase (TDPase) and thiamine monophosphatase (TMPase) as well as the thiamine diphosphate-dependent enzymes, pyruvate dehydrogenase complex, α-ketoglutarate dehydrogenase (αKGDH) and transketolase. Reductions in enzyme activities are present both in affected areas of AD brain as well as in relatively well conserved tissue. Decreased TDP concentrations and concomitantly increased TMP in autopsied brain tissue from AD patients and in CSF from patients with Dementia of the Alzheimer Type suggests that CNS thiamine phosphorylation-dephosphorylation mechanisms are disrupted in AD. αKGDH is a rate-limiting enzyme for cerebral glucose utilization and decreases in its activity are associated with lactic acidosis, cerebral energy failure and neuronal cell loss. Deficiencies of TDP-related metabolic processes could therefore participate in neuronal cell death mechanisms in AD.

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Authors and Affiliations

  1. Neuroscience Research Unit, Hôpital Saint-Luc (University of Montreal), 1058 St-Denis, H2X 3J4, Montreal, Que., Canada

    Maryse Héroux, V. L. Raghavendra Rao, Joël Lavoie & Roger F. Butterworth

  2. Dept. of Pharmacology, University of Saskatchewan, Saskatoon, Sask., Canada

    J. Stephen Richardson

Authors
  1. Maryse Héroux
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  2. V. L. Raghavendra Rao
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  3. Joël Lavoie
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  4. J. Stephen Richardson
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  5. Roger F. Butterworth
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Héroux, M., Raghavendra Rao, V.L., Lavoie, J. et al. Alterations of thiamine phosphorylation and of thiamine-dependent enzymes in Alzheimer's disease. Metab Brain Dis 11, 81–88 (1996). https://doi.org/10.1007/BF02080933

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