Biochemical Society Transactions

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44th International Conference on the Bioscience of Lipids

Connection of lipid peroxide oxidation with the sphingomyelin pathway in the development of Alzheimer's disease

A.V. Alessenko, A.E. Bugrova, L.B. Dudnik


Alzheimer's disease (AD) is characterized by progressive decline in cognition, memory and intellect. It has been hypothesized that amyloid-β peptide (A-β) may have a prominent role in neurodegeneration. Oxidative mechanisms have been implicated in this pathway. There is substantial evidence that inflammatory mechanisms, induced by tumour necrosis factor α (TNF-α), are also involved in AD. TNF-α activates receptors linked to multiple effector systems, including a sphingomyelin pathway and peroxide oxidation. We have determined the changes of neutral sphingomyelinase activity, sphingomyelin and ceramide contents, and the level of lipid peroxide products (conjugated dienes), in the cerebral cortex, hippocampus and cerebellum of rats within 3 h and 7 days of intracerebral injection of A-β and TNF-α. A single injection of A-β and TNF-α has been shown to increase the level of peroxide products in the hippocampus and cerebral cortex within 3 h and 7 days. Sphingomyelinase activity and ceramide levels have been found to increase 7 days after A-β administration. We found that activation of the sphingomyelin pathway lies downstream from the oxidative stress.

  • Alzheimer's disease
  • amyloid-β peptide
  • ceramide
  • lipid peroxidation
  • tumour necrosis factor α (TNF-α)
  • sphingomyelin cycle


  • 44th International Conference on the Bioscience of Lipids, a meeting held at Keble College, Oxford, 7–11 September 2003

  • Abbreviations used: A-β, amyloid β-peptide; AD, Alzheimer's disease; SPM, sphingomyelin; SPMase, sphingomyelinase; TNF-α, tumour necrosis factor α.