Increased ceramide in brains with alzheimer's and other neurodegenerative diseases

Valery Filippov, Minwoo Andrew Song, Kangling Zhang, Harry V. Vinters, Spencer Tung, Wolff M. Kirsch, Jun Yang, Penelope J. Duerksen-Hughes

Research output: Contribution to journalArticle

83 Scopus citations

Abstract

Ceramide has been suggested to participate in the neuronal cell death that leads to Alzheimer's disease (AD), but its role is not yet well-understood. We compared the levels of six ceramide subspecies, which differ in the length of their fatty acid moieties, in brains from patients who suffered from AD, other neuropathological disorders, or both. We found elevated levels of Cer16, Cer18, Cer20, and Cer24 in brains from patients with any of the tested neural defects. Moreover, ceramide levels were highest in patients with more than one neuropathologic abnormality. Interestingly, the range of values was higher among brains with neural defects than in controls, suggesting that the regulation of ceramide synthesis is normally under tight control, and that this tight control may be lost during neurodegeneration. These changes, however, did not alter the ratio between the tested ceramide species. To explore the mechanisms underlying this dysregulation, we evaluated the expression of four genes connected to ceramide metabolism: ASMase, NSMase 2, GALC, and UGCG. The patterns of gene expression were complex, but overall, ASMase, NSMase 2, and GALC were upregulated in specimens from patients with neuropathologic abnormalities in comparison with age-matched controls. Such findings suggest these genes as attractive candidates both for diagnostic purposes and for intervening in neurodegenerative processes.

Original languageEnglish (US)
Pages (from-to)537-547
Number of pages11
JournalJournal of Alzheimer's Disease
Volume29
Issue number3
DOIs
StatePublished - 2012
Externally publishedYes

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Keywords

  • Alzheimer's disease
  • ceramide
  • neurodegeneration
  • sphingolipid biosynthesis
  • sphingolipid regulation

ASJC Scopus subject areas

  • Neuroscience(all)
  • Clinical Psychology
  • Geriatrics and Gerontology
  • Psychiatry and Mental health

Cite this

Filippov, V., Song, M. A., Zhang, K., Vinters, H. V., Tung, S., Kirsch, W. M., Yang, J., & Duerksen-Hughes, P. J. (2012). Increased ceramide in brains with alzheimer's and other neurodegenerative diseases. Journal of Alzheimer's Disease, 29(3), 537-547. https://doi.org/10.3233/JAD-2011-111202