University of IcelandTeitsdóttir, Unnur DiljáHalldórsson, SkarphéðinnRolfsson, ÓttarLund, Sigrún H.Jónsdóttir, María KristínSnædal, Jón G.Petersen, Pétur Henry2025-11-202025-11-202021-05-04Teitsdóttir, U D, Halldórsson, S, Rolfsson, Ó, Lund, S H, Jónsdóttir, M K, Snædal, J G & Petersen, P H 2021, 'Cerebrospinal Fluid C18 Ceramide Associates with Markers of Alzheimer's Disease and Inflammation at the Pre- And Early Stages of Dementia', Journal of Alzheimer's Disease, vol. 81, no. 1, pp. 231-244. https://doi.org/10.3233/JAD-2009641387-287737250141dc9e28ab-3dd6-4bca-ae87-48d9663ffae88510572343633814423unpaywall: 10.3233/jad-200964https://hdl.handle.net/20.500.11815/6289Funding Information: This study was supported by the St. Josef´s Hospital Fund, Reykjavik, Iceland, the Landspitali University Hospital Research Fund and the Icelandic Research Fund of the Icelandic Centre for Research (163172-051). The authors thank all the subjects of The Icelandic MCI study for their participation. They also wish to thank Kristin H. Hannesdottir for managing participant administration and the staff of the LUH Memory Clinic. Funding Information: This study was supported by the St. Josefs Hospital Fund, Reykjavik, Iceland, the Landspitali University Hospital Research Fund and the Icelandic Research Fund of the Icelandic Centre for Research (163172-051). Publisher Copyright: © 2021 - The authors. Published by IOS Press.BACKGROUND: Understanding how dysregulation in lipid metabolism relates to the severity of Alzheimer's disease (AD) pathology might be critical in developing effective treatments. OBJECTIVE: To identify lipid species in cerebrospinal fluid (CSF) associated with signature AD pathology and to explore their relationships with measures reflecting AD-related processes (neurodegeneration, inflammation, deficits in verbal episodic memory) among subjects at the pre- and early symptomatic stages of dementia. METHODS: A total of 60 subjects that had been referred to an Icelandic memory clinic cohort were classified as having CSF AD (n = 34) or non-AD (n = 26) pathology profiles. Untargeted CSF lipidomic analysis was performed using ultra-performance liquid chromatography-tandem mass spectrometry (UPLC-MS) for the detection of mass-to-charge ratio (m/z) features. CSF proteins reflecting neurodegeneration (neurofilament light [NFL]) and inflammation (chitinase-3-like protein 1 [YKL-40], S100 calcium-binding protein B [S100B], glial fibrillary acidic protein [GFAP]) were also measured. Rey Auditory Verbal Learning (RAVLT) and Story tests were used for the assessment of verbal episodic memory. RESULTS: Eight out of 1008 features were identified as best distinguishing between the CSF profile groups. Of those, only the annotation of the m/z feature assigned to lipid species C18 ceramide was confirmed with a high confidence. Multiple regression analyses, adjusted for age, gender, and education, demonstrated significant associations of CSF core AD markers (Aβ42: st.β= -0.36, p = 0.007; T-tau: st.β= 0.41, p = 0.005) and inflammatory marker S100B (st.β= 0.51, p = 0.001) with C18 ceramide levels. CONCLUSION: Higher levels of C18 ceramide associated with increased AD pathology and inflammation, suggesting its potential value as a therapeutic target.14321180231-244eninfo:eu-repo/semantics/openAccessAlzheimer's diseasebiomarkerscerebrospinal fluidinflammationlipidomicsHumansMiddle AgedMemory, EpisodicMalePeptide Fragments/cerebrospinal fluidtau Proteins/cerebrospinal fluidAmyloid beta-Peptides/cerebrospinal fluidDisease ProgressionNeuropsychological TestsBiomarkers/cerebrospinal fluidDementia/cerebrospinal fluidTandem Mass SpectrometryInflammation/cerebrospinal fluidAged, 80 and overAlzheimer Disease/cerebrospinal fluidChromatography, LiquidFemaleAgedCeramides/cerebrospinal fluidGeriatrics and GerontologyPsychiatry and Mental HealthClinical PsychologyGeneral Neuroscience/dk/atira/pure/researchoutput/researchoutputtypes/contributiontojournal/article10.3233/JAD-200964