Astrocytic ceramide as possible indicator of neuroinflammation

Nienke M. de Wit*, Sandra den Hoedt, Pilar Martinez-Martinez, Annemieke J. Rozemuller, Monique T. Mulder, Helga E. de Vries

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review


BackgroundNeurodegenerative diseases such as Alzheimer's disease (AD), Parkinson's disease dementia (PDD), and frontotemporal lobar dementia (FTLD) are characterized by progressive neuronal loss but differ in their underlying pathological mechanisms. However, neuroinflammation is commonly observed within these different forms of dementia. Recently, it has been suggested that an altered sphingolipid metabolism may contribute to the pathogenesis of a variety of neurodegenerative conditions. Especially ceramide, the precursor of all complex sphingolipids, is thought to be associated with pro-apoptotic cellular processes, thereby propagating neurodegeneration and neuroinflammation, although it remains unclear to what extent. The current pathological study therefore investigates whether increased levels of ceramide are associated with the degree of neuroinflammation in various neurodegenerative disorders.MethodsImmunohistochemistry was performed on human post-mortem tissue of PDD and FTLD Pick's disease cases, which are well-characterized cases of dementia subtypes differing in their neuroinflammatory status, to assess the expression and localization of ceramide, acid sphingomyelinase, and ceramide synthase 2 and 5. In addition, we determined the concentration of sphingosine, sphingosine-1-phosphate (S1P), and ceramide species differing in their chain-length in brain homogenates of the post-mortem tissue using HPLC-MS/MS.ResultsOur immunohistochemical analysis reveals that neuroinflammation is associated with increased ceramide levels in astrocytes in FTLD Pick's disease. Moreover, the observed increase in ceramide in astrocytes correlates with the expression of ceramide synthase 5. In addition, HPLC-MS/MS analysis shows a shift in ceramide species under neuroinflammatory conditions, favoring pro-apoptotic ceramide.ConclusionsTogether, these findings suggest that detected increased levels of pro-apoptotic ceramide might be a common denominator of neuroinflammation in different neurodegenerative diseases.

Original languageEnglish
Article number48
Number of pages11
JournalJournal of Neuroinflammation
Publication statusPublished - 25 Feb 2019


  • Neuroinflammation
  • Neurodegenerative diseases
  • Sphingolipids
  • Ceramide
  • Ceramide synthase
  • Acid sphingomyelinase

Cite this