AbstractThiamin plays a key role in the maintenance of brain function. Thiamin diphosphate is cofactor for several enzymes involved in glucose metabolism whereas thiamin triphosphate has distinct properties at the neuronal membrane. Thiamin metabolism in the brain is compartmented between neurons and neighbouring glial cells. Thiamin deficiency is commonly encountered in severe malnutrition associated with chronic alcoholism, HIV–AIDS and gastrointestinal disease where it frequently results in Wernicke's encephalopathy (the Wernicke–Korsakoff syndrome). Wernicke's encephalopathy is severely underdiagnosed according to clinical criteria in both alcoholic and HIV–AIDS patients. Magnetic resonance imaging reveals bilateral ventricular enlargement, mammillary body atrophy and cerebellar degeneration indicative of selective neuronal loss that is characteristic of Wernicke's encephalopathy. Several mechanisms have been proposed to explain this selective loss of neurons including a cerebral energy deficit resulting from reductions in activity of thiamin diphosphate-dependent enzymes, oxidative stress and N-methyl-D-aspartate receptor-mediated excitotoxicity. Both microglia and perivascular endothelial cells are sources of NO and oxidative stress in thiamin deficiency. Decreased activities of thiamin diphosphate-dependent enzymes (in particular α-ketoglutarate dehydrogenase) have also been reported in neurodegenerative diseases such as Alzheimer's and Parkinson's diseases independent of patient malnutrition. In these cases, decreased activities result from direct toxic actions of oxidative stress and β-amyloid produced as part of the neuronal cell death cascade in these disorders.