Opin vísindi

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

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


Title: Association of glial and neuronal degeneration markers with Alzheimer’s disease cerebrospinal fluid profile and cognitive functions
Author: Teitsdóttir, Unnur Diljá   orcid.org/0000-0003-2723-2242
Jónsdóttir, María K.
Lund, Sigrún Helga   orcid.org/0000-0002-3806-2296
Darreh-Shori, Taher
Snædal, Jón
Petersen, Petur Henry   orcid.org/0000-0001-6622-3002
Date: 2020-08-04
Language: English
Scope: 12-92
University/Institute: Háskólinn í Reykjavík
Reykjavik University
Háskóli Íslands
University of Iceland
School: Samfélagssvið (HR)
School of Social Sciences (RU)
Heilbrigðisvísindasvið (HÍ)
School of Health Sciences (UI)
Department: Sálfræðideild (HR)
Department of Psychology (RU)
Læknadeild (HÍ)
Faculty of Medicine (UI)
Lífvísindasetur (HÍ)
Biomedical Center (UI)
Series: Alzheimer's Research & Therapy;12(1)
ISSN: 1758-9193
DOI: 10.1186/s13195-020-00657-8
Subject: Cognitive Neuroscience; Neurology; Clinical Neurology; Alzheimer’s disease; Neurofilament light,; Cerebrospinal fluid; YKL-40; S100 calcium-binding protein B; Glialfibrillary acidic protein; AD biomarker profile; Cognitive domains; Taugavísindi; Taugalækningar; Alzheimer sjúkdómur; Mænuvökvi; Prótín
URI: https://hdl.handle.net/20.500.11815/2280

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Citation:

Teitsdottir, U. D., Jonsdottir, M. K., Lund, S. H., Darreh-Shori, T., Snaedal, J., & Petersen, P. H. (2020). Association of glial and neuronal degeneration markers with Alzheimer’s disease cerebrospinal fluid profile and cognitive functions. Alzheimers Research & Therapy, 12(1), 92. https://doi.org/10.1186/s13195-020-00657-8

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

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© The Author(s). 2020 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, visithttp://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.

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