ALTERATIONS OF THIAMINE PHOSPHORYLATION AND OF THIAMINE-DEPENDENT ENZYMES IN ALZHEIMERS-DISEASE

There is a growing body of evidence to suggest that thiamine neurochem istry is disrupted in Alzheimer's Disease (AD). Studies in autopsied b rain tissue from neuropathologically proven AD patients reveal signifi cantly reduced activities of the thiamine phosphate dephosphorylating enzymes thiamine diphosphatase (TDPase) and thiamine monophosphatase ( TMPase) as well as the thiamine diphosphate-dependent enzymes, pyruvat e dehydrogenase complex, alpha-ketoglutarate dehydrogenase (alpha KGDH ) 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 i n autopsied brain tissue from AD patients and in CSF from patients wit h Dementia of the Alzheimer Type suggests that CNS thiamine phosphoryl ation-dephosphorylation mechanisms are disrupted in AD. alpha KGDH is a rate-limiting enzyme for cerebral glucose utilization and decreases in its activity are associated with lactic acidosis, cerebral energy f ailure and neuronal cell loss. Deficiencies of TDP-related metabolic p rocesses could therefore participate in neuronal cell death mechanisms in AD.