title: Peripheral sphingolipids are associated with variation in white matter microstructure in older adults.
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.
authors.affiliation: Laboratory of Behavioral Neuroscience, Intramural Research Program, National Institute on Aging, National Institutes of Health, Baltimore, MD, USA.
authors.forename: Christopher E
authors.initials: CE
authors.lastname: Gonzalez
authors.affiliation: Laboratory of Behavioral Neuroscience, Intramural Research Program, National Institute on Aging, National Institutes of Health, Baltimore, MD, USA.
authors.forename: Vijay K
authors.initials: VK
authors.lastname: Venkatraman
authors.affiliation: Laboratory of Behavioral Neuroscience, Intramural Research Program, National Institute on Aging, National Institutes of Health, Baltimore, MD, USA.
authors.forename: Yang
authors.initials: Y
authors.lastname: An
authors.affiliation: Institute of Imaging Science and Department of Electrical Engineering, Vanderbilt University, Nashville, TN, USA.
authors.forename: Bennett A
authors.initials: BA
authors.lastname: Landman
authors.affiliation: Department of Radiology, University of Pennsylvania, Philadelphia, PA, USA.
authors.forename: Christos
authors.initials: C
authors.lastname: Davatzikos
authors.affiliation: Department of Neurology, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
authors.forename: Veera Venkata
authors.initials: VV
authors.lastname: Ratnam Bandaru
authors.affiliation: Department of Neurology, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
authors.forename: Norman J
authors.initials: NJ
authors.lastname: Haughey
authors.affiliation: Laboratory of Behavioral Neuroscience, Intramural Research Program, National Institute on Aging, National Institutes of Health, Baltimore, MD, USA.
authors.forename: Luigi
authors.initials: L
authors.lastname: Ferrucci
authors.affiliation: Department of Health Science Research, Mayo Clinic, Rochester, MN, USA; Department of Neurology, Mayo Clinic, Rochester, MN, USA. Electronic address: mielke.michelle@mayo.edu.
authors.forename: Michelle M
authors.initials: MM
authors.lastname: Mielke
authors.affiliation: Laboratory of Behavioral Neuroscience, Intramural Research Program, National Institute on Aging, National Institutes of Health, Baltimore, MD, USA.
authors.forename: Susan M
authors.initials: SM
authors.lastname: Resnick
mesh_terms: D000368:Aged; D000375:Aging / Q000378:metabolism* / Q000473:pathology*; D016880:Anisotropy; D002518:Ceramides / Q000097:blood; D003071:Cognition; D038524:Diffusion Magnetic Resonance Imaging; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D013107:Sphingolipids / Q000097:blood*; D013109:Sphingomyelins / Q000097:blood; D066127:White Matter / Q000000981:diagnostic imaging* / Q000378:metabolism / Q000473:pathology* / Q000503:physiopathology
chemical_list: D002518:Ceramides; D013107:Sphingolipids; D013109:Sphingomyelins
keywords: Ceramides; DTI; Fractional anisotropy; Sphingolipids; Sphingomyelin; White matter