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Association of glial and neuronal degeneration markers with Alzheimer’s disease cerebrospinal fluid profile and cognitive functions

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dc.contributor Háskóli Íslands
dc.contributor University of Iceland
dc.contributor Háskólinn í Reykjavík
dc.contributor Reykjavik University
dc.contributor.author Teitsdóttir, Unnur Diljá
dc.contributor.author Jónsdóttir, María K.
dc.contributor.author Lund, Sigrún H.
dc.contributor.author Darreh-Shori, Taher
dc.contributor.author Snædal, Jón
dc.contributor.author Petersen, Pétur H.
dc.date.accessioned 2020-11-30T15:29:18Z
dc.date.available 2020-11-30T15:29:18Z
dc.date.issued 2020-08-04
dc.identifier.citation Teitsdottir, U.D., Jonsdottir, M.K., Lund, S.H. et al. Association of glial and neuronal degeneration markers with Alzheimer’s disease cerebrospinal fluid profile and cognitive functions. Alzheimer's Research & Therapy 12, 92 (2020). https://doi.org/10.1186/s13195-020-00657-8
dc.identifier.issn 1758-9193
dc.identifier.uri https://hdl.handle.net/20.500.11815/2260
dc.description Publisher's version (útgefin grein)
dc.description.abstract Background: Neuroinflammation has gained increasing attention as a potential contributing factor in the onset and progression of Alzheimer's disease (AD). The objective of this study was to examine the association of selected cerebrospinal fluid (CSF) inflammatory and neuronal degeneration markers with signature CSF AD profile and cognitive functions among subjects at the symptomatic pre- and early dementia stages. Methods: In this cross-sectional study, 52 subjects were selected from an Icelandic memory clinic cohort. Subjects were classified as having AD (n = 28, age = 70, 39% female, Mini-Mental State Examination [MMSE] = 27) or non-AD (n = 24, age = 67, 33% female, MMSE = 28) profile based on the ratio between CSF total-tau (T-tau) and amyloid-β1-42 (Aβ42) values (cut-off point chosen as 0.52). Novel CSF biomarkers included neurofilament light (NFL), YKL-40, S100 calcium-binding protein B (S100B) and glial fibrillary acidic protein (GFAP), measured with enzyme-linked immunosorbent assays (ELISAs). Subjects underwent neuropsychological assessment for evaluation of different cognitive domains, including verbal episodic memory, non-verbal episodic memory, language, processing speed, and executive functions. Results: Accuracy coefficient for distinguishing between the two CSF profiles was calculated for each CSF marker and test. Novel CSF markers performed poorly (area under curve [AUC] coefficients ranging from 0.61 to 0.64) compared to tests reflecting verbal episodic memory, which all performed fair (AUC > 70). LASSO regression with a stability approach was applied for the selection of CSF markers and demographic variables predicting performance on each cognitive domain, both among all subjects and only those with a CSF AD profile. Relationships between CSF markers and cognitive domains, where the CSF marker reached stability selection criteria of > 75%, were visualized with scatter plots. Before calculations of corresponding Pearson's correlations coefficients, composite scores for cognitive domains were adjusted for age and education. GFAP correlated with executive functions (r = - 0.37, p = 0.01) overall, while GFAP correlated with processing speed (r = - 0.68, p < 0.001) and NFL with verbal episodic memory (r = - 0.43, p = 0.02) among subjects with a CSF AD profile. Conclusions: The novel CSF markers NFL and GFAP show potential as markers for cognitive decline among individuals with core AD pathology at the symptomatic pre- and early stages of dementia.
dc.description.sponsorship This study was funded 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).
dc.format.extent 92
dc.language.iso en
dc.publisher Springer Science and Business Media LLC
dc.relation.ispartofseries Alzheimer's Research & Therapy;12(1)
dc.rights info:eu-repo/semantics/openAccess
dc.subject AD biomarker profile
dc.subject Alzheimer's disease
dc.subject Cerebrospinal fluid
dc.subject Cognitive domains
dc.subject Glial fibrillary acidic protein
dc.subject Neurofilament light
dc.subject S100 calcium-binding protein B
dc.subject YKL-40
dc.subject Alzheimer sjúkdómur
dc.title Association of glial and neuronal degeneration markers with Alzheimer’s disease cerebrospinal fluid profile and cognitive functions
dc.type info:eu-repo/semantics/article
dcterms.license Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated in a credit line to the data.
dc.description.version Peer Reviewed
dc.identifier.journal Alzheimer's Research & Therapy
dc.identifier.doi 10.1186/s13195-020-00657-8
dc.relation.url https://alzres.biomedcentral.com/articles/10.1186/s13195-020-00657-8
dc.contributor.department Læknadeild (HÍ)
dc.contributor.department Faculty of Medicine (UI)
dc.contributor.department Lífvísindasetur (HÍ)
dc.contributor.department Biomedical Center (UI)
dc.contributor.department Sálfræðideild (HR)
dc.contributor.department Department of Psychology (RU)
dc.contributor.school Heilbrigðisvísindasvið (HÍ)
dc.contributor.school School of Health Sciences (UI)
dc.contributor.school Samfélagssvið (HR)
dc.contributor.school Samfélagssvið: School of Social Sciences (RU)

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