Peripheral sphingolipids are associated with variation in white matter microstructure in older adults

Christopher E. Gonzalez, Vijay K. Venkatraman, Yang An, Bennett A. Landman, Christos Davatzikos, Veera Venkata Ratnam Bandaru, Norman J. Haughey, Luigi Ferrucci, Michelle M Mielke, Susan M. Resnick

Research output: Contribution to journalArticle

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Abstract

Sphingolipids serve important structural and functional roles in cellular membranes and myelin sheaths. Plasma sphingolipids have been shown to predict cognitive decline and Alzheimer's disease. However, the association between plasma sphingolipid levels and brain white matter (WM) microstructure has not been examined. We investigated whether plasma sphingolipids (ceramides and sphingomyelins) were associated with magnetic resonance imaging-based diffusion measures, fractional anisotropy (FA), and mean diffusivity, 10.5 years later in 17 WM regions of 150 cognitively normal adults (mean age 67.2). Elevated ceramide species (C20:0, C22:0, C22:1, and C24:1) were associated with lower FA in multiple WM regions, including total cerebral WM, anterior corona radiata, and the cingulum of the cingulate gyrus. Higher sphingomyelins (C18:1 and C20:1) were associated with lower FA in regions such as the anterior corona radiata and body of the corpus callosum. Furthermore, lower sphingomyelin to ceramide ratios (C22:0, C24:0, and C24:1) were associated with lower FA or higher mean diffusivity in regions including the superior and posterior corona radiata. However, although these associations were significant at the a priori p <0.05, only associations with some regional diffusion measures for ceramide C22:0 and sphingomyelin C18:1 survived correction for multiple comparisons. These findings suggest plasma sphingolipids are associated with variation in WM microstructure in cognitively normal aging.

Original languageEnglish (US)
Pages (from-to)156-163
Number of pages8
JournalNeurobiology of Aging
Volume43
DOIs
StatePublished - Jul 1 2016

Fingerprint

Sphingolipids
Sphingomyelins
Anisotropy
Ceramides
Diffusion Magnetic Resonance Imaging
Corpus Callosum
Gyrus Cinguli
Myelin Sheath
Alzheimer Disease
White Matter
Membranes
Brain

Keywords

  • Ceramides
  • DTI
  • Fractional anisotropy
  • Sphingolipids
  • Sphingomyelin
  • White matter

ASJC Scopus subject areas

  • Clinical Neurology
  • Neuroscience(all)
  • Aging
  • Developmental Biology
  • Geriatrics and Gerontology

Cite this

Gonzalez, C. E., Venkatraman, V. K., An, Y., Landman, B. A., Davatzikos, C., Ratnam Bandaru, V. V., ... Resnick, S. M. (2016). Peripheral sphingolipids are associated with variation in white matter microstructure in older adults. Neurobiology of Aging, 43, 156-163. https://doi.org/10.1016/j.neurobiolaging.2016.04.008

Peripheral sphingolipids are associated with variation in white matter microstructure in older adults. / Gonzalez, Christopher E.; Venkatraman, Vijay K.; An, Yang; Landman, Bennett A.; Davatzikos, Christos; Ratnam Bandaru, Veera Venkata; Haughey, Norman J.; Ferrucci, Luigi; Mielke, Michelle M; Resnick, Susan M.

In: Neurobiology of Aging, Vol. 43, 01.07.2016, p. 156-163.

Research output: Contribution to journalArticle

Gonzalez, CE, Venkatraman, VK, An, Y, Landman, BA, Davatzikos, C, Ratnam Bandaru, VV, Haughey, NJ, Ferrucci, L, Mielke, MM & Resnick, SM 2016, 'Peripheral sphingolipids are associated with variation in white matter microstructure in older adults', Neurobiology of Aging, vol. 43, pp. 156-163. https://doi.org/10.1016/j.neurobiolaging.2016.04.008
Gonzalez, Christopher E. ; Venkatraman, Vijay K. ; An, Yang ; Landman, Bennett A. ; Davatzikos, Christos ; Ratnam Bandaru, Veera Venkata ; Haughey, Norman J. ; Ferrucci, Luigi ; Mielke, Michelle M ; Resnick, Susan M. / Peripheral sphingolipids are associated with variation in white matter microstructure in older adults. In: Neurobiology of Aging. 2016 ; Vol. 43. pp. 156-163.
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abstract = "Sphingolipids serve important structural and functional roles in cellular membranes and myelin sheaths. Plasma sphingolipids have been shown to predict cognitive decline and Alzheimer's disease. However, the association between plasma sphingolipid levels and brain white matter (WM) microstructure has not been examined. We investigated whether plasma sphingolipids (ceramides and sphingomyelins) were associated with magnetic resonance imaging-based diffusion measures, fractional anisotropy (FA), and mean diffusivity, 10.5 years later in 17 WM regions of 150 cognitively normal adults (mean age 67.2). Elevated ceramide species (C20:0, C22:0, C22:1, and C24:1) were associated with lower FA in multiple WM regions, including total cerebral WM, anterior corona radiata, and the cingulum of the cingulate gyrus. Higher sphingomyelins (C18:1 and C20:1) were associated with lower FA in regions such as the anterior corona radiata and body of the corpus callosum. Furthermore, lower sphingomyelin to ceramide ratios (C22:0, C24:0, and C24:1) were associated with lower FA or higher mean diffusivity in regions including the superior and posterior corona radiata. However, although these associations were significant at the a priori p <0.05, only associations with some regional diffusion measures for ceramide C22:0 and sphingomyelin C18:1 survived correction for multiple comparisons. These findings suggest plasma sphingolipids are associated with variation in WM microstructure in cognitively normal aging.",
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