Circulating sphingolipids and subclinical brain pathology: the cardiovascular health study.
| Autor: | Moseholm KF; Department of Public Health, Section of Epidemiology, University of Copenhagen, Copenhagen, Denmark., Horn JW; Department of Internal Medicine, Levanger Hospital, Health Trust Nord-Trøndelag, Levanger, Norway., Fitzpatrick AL; Departments of Family Medicine and Epidemiology, School of Public Health, University of Washington, Seattle, WA, United States., Djoussé L; Division of Aging, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA, United States.; Department of Nutrition, Harvard T.H. Chan School of Public Health, Boston, MA, United States., Longstreth WT Jr; Departments of Family Medicine and Epidemiology, School of Public Health, University of Washington, Seattle, WA, United States.; Department of Neurology, School of Medicine, University of Washington, Seattle, WA, United States., Lopez OL; Department of Neurology, School of Medicine, University of Pittsburgh, Pittsburgh, PA, United States., Hoofnagle AN; Department of Laboratory Medicine and Pathology, School of Medicine, University of Washington, Seattle, WA, United States., Jensen MK; Department of Public Health, Section of Epidemiology, University of Copenhagen, Copenhagen, Denmark.; Department of Nutrition, Harvard T.H. Chan School of Public Health, Boston, MA, United States., Lemaitre RN; Cardiovascular Health Research Unit, Department of Medicine, University of Washington, Seattle, WA, United States., Mukamal KJ; Department of Medicine, Beth Israel Deaconess Medical Center, Boston, MA, United States. |
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| Jazyk: | angličtina |
| Zdroj: | Frontiers in neurology [Front Neurol] 2024 May 03; Vol. 15, pp. 1385623. Date of Electronic Publication: 2024 May 03 (Print Publication: 2024). |
| DOI: | 10.3389/fneur.2024.1385623 |
| Abstrakt: | Background: Sphingolipids are implicated in neurodegeneration and neuroinflammation. We assessed the potential role of circulating ceramides and sphingomyelins in subclinical brain pathology by investigating their association with brain magnetic resonance imaging (MRI) measures and circulating biomarkers of brain injury, neurofilament light chain (NfL) and glial fibrillary acidic protein (GFAP) in the Cardiovascular Health Study (CHS), a large and intensively phenotyped cohort of older adults. Methods: Brain MRI was offered twice to CHS participants with a mean of 5 years between scans, and results were available from both time points in 2,116 participants (mean age 76 years; 40% male; and 25% APOE ε4 allele carriers). We measured 8 ceramide and sphingomyelin species in plasma samples and examined the associations with several MRI, including worsening grades of white matter hyperintensities and ventricular size, number of brain infarcts, and measures of brain atrophy in a subset with quantitative measures. We also investigated the sphingolipid associations with serum NfL and GFAP. Results: In the fully adjusted model, higher plasma levels of ceramides and sphingomyelins with a long (16-carbon) saturated fatty acid were associated with higher blood levels of NfL [β = 0.05, false-discovery rate corrected P ( P Conclusion: Overall, our comprehensive investigation supports the evidence that ceramides and sphingomyelins are associated with increased aging brain pathology and that the direction of association depends on the fatty acid attached to the sphingosine backbone. Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. (Copyright © 2024 Moseholm, Horn, Fitzpatrick, Djoussé, Longstreth, Lopez, Hoofnagle, Jensen, Lemaitre and Mukamal.) |
| Databáze: | MEDLINE |
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