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dc.contributor.authorTeitsdottir, Unnur D
dc.contributor.authorJonsdottir, Maria K
dc.contributor.authorLund, Sigrun H
dc.contributor.authorDarreh-Shori, Taher
dc.contributor.authorSnaedal, Jon
dc.contributor.authorPetersen, Petur H
dc.date.accessioned2020-09-09T11:11:59Z
dc.date.available2020-09-09T11:11:59Z
dc.date.issued2020-08-04
dc.date.submitted2020-09
dc.identifier.citationTeitsdottir UD, Jonsdottir MK, Lund SH, Darreh-Shori T, Snaedal J, Petersen PH. Association of glial and neuronal degeneration markers with Alzheimer's disease cerebrospinal fluid profile and cognitive functions. Alzheimers Res Ther. 2020;12(1):92. Published 2020 Aug 4. doi:10.1186/s13195-020-00657-8en_US
dc.identifier.pmid32753068
dc.identifier.doi10.1186/s13195-020-00657-8
dc.identifier.urihttp://hdl.handle.net/2336/621521
dc.descriptionTo access publisher's full text version of this article, please click on the hyperlink in Additional Links field or click on the hyperlink at the top of the page marked Downloaden_US
dc.description.abstractBackground: 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. Keywords: AD biomarker profile; Alzheimer’s disease; Cerebrospinal fluid; Cognitive domains; Glial fibrillary acidic protein; Neurofilament light; S100 calcium-binding protein B; YKL-40.en_US
dc.description.sponsorshipSt. Josef's Hospital Fund, Reykjavik, Iceland Landspitali University Hospital Research Fund Icelandic Research Fund of the Icelandic Centre for Researchen_US
dc.language.isoenen_US
dc.publisherBioMed Centralen_US
dc.relation.urlhttps://alzres.biomedcentral.com/articles/10.1186/s13195-020-00657-8en_US
dc.relation.urlhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC7404927/en_US
dc.subjectAD biomarker profileen_US
dc.subjectAlzheimer’s diseaseen_US
dc.subjectCerebrospinal fluiden_US
dc.subjectCognitive domainsen_US
dc.subjectGlial fibrillary acidic proteinen_US
dc.subjectNeurofilament lighten_US
dc.subjectS100 calcium-binding protein Ben_US
dc.subjectYKL-40en_US
dc.subjectAlzheimer sjúkdómuren_US
dc.titleAssociation of glial and neuronal degeneration markers with Alzheimer's disease cerebrospinal fluid profile and cognitive functions.en_US
dc.typeArticleen_US
dc.typeOtheren_US
dc.identifier.eissn1758-9193
dc.contributor.department1Faculty of Medicine, Department of Anatomy, Biomedical Center, University of Iceland, Reykjavik, Iceland. udt1@hi.is. 2Department of Psychology, Reykjavik University, Reykjavik, Iceland. 3Department of Psychiatry, Landspitali - National University Hospital, Reykjavik, Iceland. 4deCODE genetics/Amgen, Inc., Reykjavik, Iceland. 5Division of Clinical Geriatrics, Center for Alzheimer Research, NVS Department, Karolinska Institutet, Huddinge, Sweden. 6Memory clinic, Department of Geriatric Medicine, Landspitali - National University Hospital, Reykjavik, Iceland. 7Faculty of Medicine, Department of Anatomy, Biomedical Center, University of Iceland, Reykjavik, Iceland.en_US
dc.identifier.journalAlzheimer's research & therapyen_US
dc.rights.accessOpen Access - Opinn aðganguren_US
dc.departmentcodePSC12
dc.departmentcodeGER12
dc.source.journaltitleAlzheimer's research & therapy
dc.source.volume12
dc.source.issue1
dc.source.beginpage92
dc.source.endpage
refterms.dateFOA2020-09-09T11:11:59Z
dc.source.countryEngland


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