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Thiamine-dependent processes and treatment strategies in neurodegeneration.

Research paper by Gary E GE Gibson, John P JP Blass

Indexed on: 10 Aug '07Published on: 10 Aug '07Published in: Antioxidants & redox signaling



Abstract

Reductions in brain glucose metabolism and increased oxidative stress invariably occur in Alzheimer's disease (AD) and thiamine (vitamin B1) deficiency. Both conditions cause irreversible cognitive impairment; their behavioral consequences overlap but are not identical. Thiamine-dependent processes are critical in glucose metabolism, and recent studies implicate thiamine in oxidative stress, protein processing, peroxisomal function, and gene expression. The activities of thiamine-dependent enzymes are characteristically diminished in AD, and the reductions in autopsy AD brain correlate highly with the extent of dementia in the preagonal state. Abnormalities in thiamine-dependent processes can be plausibly linked to the pathology of AD. Seemingly paradoxical properties of thiamine-dependent processes may underlie their relation to the pathophysiology of AD: Reduction of thiamine-dependent processes increase oxidative stress. Thiamine can act as a free radical scavenger. Thiamine-dependent mitochondrial dehydrogenase complexes produce oxygen free radicals and are sensitive to oxidative stress. Genetic disorders of thiamine metabolism that lead to neurological disease can be treated with large doses of thiamine. Although thiamine itself has not shown dramatic benefits in AD patients, the available data is scanty. Adding thiamine or more absorbable forms of thiamine to tested treatments for the abnormality in glucose metabolism in AD may increase their efficacy.