Cerebrospinal Fluid C18 Ceramide Associates with Markers of Alzheimer's Disease and Inflammation at the Pre- And Early Stages of Dementia

• Published in: Journal of Alzheimer's Disease
• Main Authors: Teitsdóttir, Unnur Diljá, Halldórsson, Skarphéðinn, Rolfsson, Óttar, Lund, Sigrún H., Jónsdóttir, María Kristín, Snædal, Jón G., Petersen, Pétur Henry
• Other Authors: Faculty of Medicine, Faculty of Physical Sciences, Mental Health Services, Geriatric and Rehabilitation Services, University of Iceland, Landspitali - The National University Hospital of Iceland, Reykjavik University
• Format: Article in Journal/Newspaper
• Language: English
• Published: 2021
• Subjects: Alzheimer sjúkdómur; Bólgur; Lífmerki; Alzheimer's disease; biomarkers; cerebrospinal fluid; inflammation; lipidomics; Humans; Middle Aged; Memory; Episodic; Male; Peptide Fragments/cerebrospinal fluid; tau Proteins/cerebrospinal fluid; Amyloid beta-Peptides/cerebrospinal fluid; Disease Progression; Neuropsychological Tests; Biomarkers/cerebrospinal fluid; Dementia/cerebrospinal fluid; Tandem Mass Spectrometry; Inflammation/cerebrospinal fluid; Aged; 80 and over; Alzheimer Disease/cerebrospinal fluid; Chromatography; Liquid; Female; Ceramides/cerebrospinal fluid; Geriatrics and Gerontology; Psychiatry and Mental Health; Clinical Psychology; Neuroscience (all); Iceland
• Online Access: https://hdl.handle.net/20.500.11815/2957; https://doi.org/10.3233/JAD-200964

Funding 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 ...