Circulating sphingolipids and subclinical brain pathology: the cardiovascular health study
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Circulating sphingolipids and subclinical brain pathology : the cardiovascular health study. / Moseholm, Kristine F.; Horn, Jens W.; Fitzpatrick, Annette L.; Djoussé, Luc; Longstreth, W. T.; Lopez, Oscar L.; Hoofnagle, Andrew N.; Jensen, Majken K.; Lemaitre, Rozenn N.; Mukamal, Kenneth J.
I: Frontiers in Neurology, Bind 15, 1385623, 2024.Publikation: Bidrag til tidsskrift › Tidsskriftartikel › Forskning › fagfællebedømt
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TY - JOUR
T1 - Circulating sphingolipids and subclinical brain pathology
T2 - the cardiovascular health study
AU - Moseholm, Kristine F.
AU - Horn, Jens W.
AU - Fitzpatrick, Annette L.
AU - Djoussé, Luc
AU - Longstreth, W. T.
AU - Lopez, Oscar L.
AU - Hoofnagle, Andrew N.
AU - Jensen, Majken K.
AU - Lemaitre, Rozenn N.
AU - Mukamal, Kenneth J.
N1 - Publisher Copyright: Copyright © 2024 Moseholm, Horn, Fitzpatrick, Djoussé, Longstreth, Lopez, Hoofnagle, Jensen, Lemaitre and Mukamal.
PY - 2024
Y1 - 2024
N2 - 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 (PFDR) = 0.004 and β = 0.06, PFDR = < 0.001, respectively]. In contrast, sphingomyelins with very long (20- and 22-carbon) saturated fatty acids tended to have an inverse association with levels of circulating NfL. In secondary analyses, we found an interaction between ceramide d18:1/20:0 and sex (P for interaction = <0.001), such that ceramide d18:1/20:0 associated with higher odds for infarcts in women [OR = 1.26 (95%CI: 1.07, 1.49), PFDR = 0.03]. We did not observe any associations with GFAP blood levels, white matter grade, ventricular grade, mean bilateral hippocampal volume, or total brain volume. 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.
AB - 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 (PFDR) = 0.004 and β = 0.06, PFDR = < 0.001, respectively]. In contrast, sphingomyelins with very long (20- and 22-carbon) saturated fatty acids tended to have an inverse association with levels of circulating NfL. In secondary analyses, we found an interaction between ceramide d18:1/20:0 and sex (P for interaction = <0.001), such that ceramide d18:1/20:0 associated with higher odds for infarcts in women [OR = 1.26 (95%CI: 1.07, 1.49), PFDR = 0.03]. We did not observe any associations with GFAP blood levels, white matter grade, ventricular grade, mean bilateral hippocampal volume, or total brain volume. 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.
KW - brain infarcts
KW - ceramide
KW - glial fibrillary acidic protein
KW - hippocampal atrophy
KW - neurofilament light chain
KW - sphingomyelin
KW - ventricular size
KW - white matter hyperintensity
U2 - 10.3389/fneur.2024.1385623
DO - 10.3389/fneur.2024.1385623
M3 - Journal article
C2 - 38765262
AN - SCOPUS:85193466770
VL - 15
JO - Frontiers in Neurology
JF - Frontiers in Neurology
SN - 1664-2295
M1 - 1385623
ER -
ID: 392870111