Korsakoff’s syndrome, or Wernicke encephalopathy, is a serious neurological disorder occurring under conditions of thiamine deficiency. It’s usually caused by long-term abuse of alcohol, which breaks down thiamine in the body. It is characterized at autopsy by lesions in the brain stem.
Thiamine is necessary for proper glucose metabolism in the brain (1). As a B vitamin it acts as a cofactor for enzymes in the Krebs cycle including pyruvate dehydrogenase. Brain insults result when metabolism is inhibited, particularly where there is high demand for energy.
A cascade of injury to the brain occurs when neuronal death reduces production of succinate and GABA as well as neuron stimulation. Without functioning pyruvate dehydrogenase, lactic acid production increases. Nucleotide synthesis and NADPH production is reduced, which in turn reduces glutathione in blood cells.
Individuals carrying apolipoprotein E (ApoE) epsilon 4 (E4) allele are at higher risk of Korsakoff’s syndrome (2). Thus, the ApoE4 genotype is associated with higher risk of Alzheimer’s disease may also be at higher risk of “alcoholic dementia”. These apolipoproteins are protein moietys of a lipoprotein, which transport lipids in the blood.
1. Salan, PN. Emedicine from WebMD. Wernicke Encephalopathy. 2009. Available at: http://emedicine.medscape.com/article/794583-overview.
2. Muramatsu T, Kato M, Matsui T et al. Apolipoprotein E epsilon 4 allele distribution in Wernicke-Korsakoff syndrome with or without global intellectual deficits. J Neural Transm 1997;104:913-20.3.