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Metabolomics in early Alzheimer's disease: identification of altered plasma sphingolipidome using shotgun lipidomics.

Publication ,  Journal Article
Han, X; Rozen, S; Boyle, SH; Hellegers, C; Cheng, H; Burke, JR; Welsh-Bohmer, KA; Doraiswamy, PM; Kaddurah-Daouk, R
Published in: PLoS One
2011

BACKGROUND: The development of plasma biomarkers could facilitate early detection, risk assessment and therapeutic monitoring in Alzheimer's disease (AD). Alterations in ceramides and sphingomyelins have been postulated to play a role in amyloidogensis and inflammatory stress related neuronal apoptosis; however few studies have conducted a comprehensive analysis of the sphingolipidome in AD plasma using analytical platforms with accuracy, sensitivity and reproducibility. METHODS AND FINDINGS: We prospectively analyzed plasma from 26 AD patients (mean MMSE 21) and 26 cognitively normal controls in a non-targeted approach using multi-dimensional mass spectrometry-based shotgun lipidomics to determine the levels of over 800 molecular species of lipids. These data were then correlated with diagnosis, apolipoprotein E4 genotype and cognitive performance. Plasma levels of species of sphingolipids were significantly altered in AD. Of the 33 sphingomyelin species tested, 8 molecular species, particularly those containing long aliphatic chains such as 22 and 24 carbon atoms, were significantly lower (p<0.05) in AD compared to controls. Levels of 2 ceramide species (N16:0 and N21:0) were significantly higher in AD (p<0.05) with a similar, but weaker, trend for 5 other species. Ratios of ceramide to sphingomyelin species containing identical fatty acyl chains differed significantly between AD patients and controls. MMSE scores were correlated with altered mass levels of both N20:2 SM and OH-N25:0 ceramides (p<0.004) though lipid abnormalities were observed in mild and moderate AD. Within AD subjects, there were also genotype specific differences. CONCLUSIONS: In this prospective study, we used a sensitive multimodality platform to identify and characterize an essentially uniform but opposite pattern of disruption in sphingomyelin and ceramide mass levels in AD plasma. Given the role of brain sphingolipids in neuronal function, our findings provide new insights into the AD sphingolipidome and the potential use of metabolomic signatures as peripheral biomarkers.

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Published In

PLoS One

DOI

EISSN

1932-6203

Publication Date

2011

Volume

6

Issue

7

Start / End Page

e21643

Location

United States

Related Subject Headings

  • Sphingolipids
  • Prospective Studies
  • Middle Aged
  • Metabolomics
  • Mass Spectrometry
  • Male
  • Humans
  • Genotype
  • General Science & Technology
  • Female
 

Citation

APA
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ICMJE
MLA
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Han, X., Rozen, S., Boyle, S. H., Hellegers, C., Cheng, H., Burke, J. R., … Kaddurah-Daouk, R. (2011). Metabolomics in early Alzheimer's disease: identification of altered plasma sphingolipidome using shotgun lipidomics. PLoS One, 6(7), e21643. https://doi.org/10.1371/journal.pone.0021643
Han, Xianlin, Steve Rozen, Stephen H. Boyle, Caroline Hellegers, Hua Cheng, James R. Burke, Kathleen A. Welsh-Bohmer, P Murali Doraiswamy, and Rima Kaddurah-Daouk. “Metabolomics in early Alzheimer's disease: identification of altered plasma sphingolipidome using shotgun lipidomics.PLoS One 6, no. 7 (2011): e21643. https://doi.org/10.1371/journal.pone.0021643.
Han X, Rozen S, Boyle SH, Hellegers C, Cheng H, Burke JR, et al. Metabolomics in early Alzheimer's disease: identification of altered plasma sphingolipidome using shotgun lipidomics. PLoS One. 2011;6(7):e21643.
Han, Xianlin, et al. “Metabolomics in early Alzheimer's disease: identification of altered plasma sphingolipidome using shotgun lipidomics.PLoS One, vol. 6, no. 7, 2011, p. e21643. Pubmed, doi:10.1371/journal.pone.0021643.
Han X, Rozen S, Boyle SH, Hellegers C, Cheng H, Burke JR, Welsh-Bohmer KA, Doraiswamy PM, Kaddurah-Daouk R. Metabolomics in early Alzheimer's disease: identification of altered plasma sphingolipidome using shotgun lipidomics. PLoS One. 2011;6(7):e21643.

Published In

PLoS One

DOI

EISSN

1932-6203

Publication Date

2011

Volume

6

Issue

7

Start / End Page

e21643

Location

United States

Related Subject Headings

  • Sphingolipids
  • Prospective Studies
  • Middle Aged
  • Metabolomics
  • Mass Spectrometry
  • Male
  • Humans
  • Genotype
  • General Science & Technology
  • Female