Cerebrospinal fluid inflammatory markers in alzheimer’s disease: Influence of comorbidities

Ying Wang; Ceren Emre; Helena Gyllenhammar-Schill; Karin Fjellman; Helga Eyjolfsdottir; Maria Eriksdotter; Marianne Schultzberg; Erik Hjorth

doi:10.2174/1567205018666210330162207

Cerebrospinal fluid inflammatory markers in alzheimer’s disease: Influence of comorbidities

Ying Wang, Ceren Emre, Helena Gyllenhammar-Schill, Karin Fjellman, Helga Eyjolfsdottir, Maria Eriksdotter, Marianne Schultzberg, Erik Hjorth^*

^*Corresponding author for this work

Research output: Contribution to journal › Article › peer-review

2 Citations (Scopus)

Abstract

Background: Alzheimer's disease (AD) develops into dementia after several years, and subjective cognitive impairment (SCI) and mild cognitive impairment (MCI) are used as intermediary diagnoses of increasing severity. Inflammation is an important part of AD pathology and provides potential novel biomarkers and treatment targets. Objective: To identify novel potential biomarkers of AD in cerebrospinal fluid (CSF) and create a molecular pattern of inflammatory factors providing differentiation between AD and SCI. Methods: We analyzed 43 inflammatory-related mediators in CSF samples from a cohort of SCI and AD cases vetted for confounding factors (Training cohort). Using multivariate analysis (MVA), a model for discrimination between SCI and AD was produced, which we then applied to a larger non-vetted cohort (named Test cohort). The data were analyzed for factors showing differences between diagnostic groups and factors that differed between the vetted and non-vetted cohorts. The relationship of the factors to the agreement between model and clinical diagnosis was investigated. Results: A good MVA model able to discriminate AD from SCI without including tangle and plaque biomarkers was produced from the Training cohort. The model showed 50% agreement with clinical diagnosis in the Test cohort. Comparison of the cohorts indicated different patterns of factors distin-guishing SCI from AD. As an example, soluble interleukin (IL)-6Rα showed lower levels in AD cases in the Training cohort, whereas placental growth factor (PlGF) and serum amyloid A (SAA) levels were higher in AD cases of the Test cohort. The levels of p-tau were also higher in the Training cohort. Conclusion: This study provides new knowledge regarding the involvement of inflammation in AD by indicating different patterns of factors in CSF depending on whether potential confounding comorbid-ities are present or not, and presents sIL-6Rα as a potential new biomarker for improved diagnosis of AD.

Original language	English
Pages (from-to)	157-170
Number of pages	14
Journal	Current Alzheimer Research
Volume	18
Issue number	2
DOIs	https://doi.org/10.2174/1567205018666210330162207
Publication status	Published - 2021

Bibliographical note

Funding Information:
The authors gratefully acknowledge the support given by the Swedish Alzheimer Foundation, the Swedish Research Council (2018-02601), Stockholm County Council (SLL20180425, RS 2019-1054), the Swedish Dementia Foundation, the China Scholarship Council (YW), the Foundation for Old Servants, the Foundation of Gun and Bertil Stohne and the Åhlén foundation.

Publisher Copyright:
© 2021 Bentham Science Publishers.

Other keywords

Alzheimer’s disease
Biomarker
Cerebrospinal fluid
Diagnosis
Inflammation
Multivariate analysis

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10.2174/1567205018666210330162207

Cite this

@article{e769d1a12b7b48edb9038c7921f86bf0,

title = "Cerebrospinal fluid inflammatory markers in alzheimer{\textquoteright}s disease: Influence of comorbidities",

abstract = "Background: Alzheimer's disease (AD) develops into dementia after several years, and subjective cognitive impairment (SCI) and mild cognitive impairment (MCI) are used as intermediary diagnoses of increasing severity. Inflammation is an important part of AD pathology and provides potential novel biomarkers and treatment targets. Objective: To identify novel potential biomarkers of AD in cerebrospinal fluid (CSF) and create a molecular pattern of inflammatory factors providing differentiation between AD and SCI. Methods: We analyzed 43 inflammatory-related mediators in CSF samples from a cohort of SCI and AD cases vetted for confounding factors (Training cohort). Using multivariate analysis (MVA), a model for discrimination between SCI and AD was produced, which we then applied to a larger non-vetted cohort (named Test cohort). The data were analyzed for factors showing differences between diagnostic groups and factors that differed between the vetted and non-vetted cohorts. The relationship of the factors to the agreement between model and clinical diagnosis was investigated. Results: A good MVA model able to discriminate AD from SCI without including tangle and plaque biomarkers was produced from the Training cohort. The model showed 50% agreement with clinical diagnosis in the Test cohort. Comparison of the cohorts indicated different patterns of factors distin-guishing SCI from AD. As an example, soluble interleukin (IL)-6Rα showed lower levels in AD cases in the Training cohort, whereas placental growth factor (PlGF) and serum amyloid A (SAA) levels were higher in AD cases of the Test cohort. The levels of p-tau were also higher in the Training cohort. Conclusion: This study provides new knowledge regarding the involvement of inflammation in AD by indicating different patterns of factors in CSF depending on whether potential confounding comorbid-ities are present or not, and presents sIL-6Rα as a potential new biomarker for improved diagnosis of AD.",

keywords = "Alzheimer{\textquoteright}s disease, Biomarker, Cerebrospinal fluid, Diagnosis, Inflammation, Multivariate analysis",

author = "Ying Wang and Ceren Emre and Helena Gyllenhammar-Schill and Karin Fjellman and Helga Eyjolfsdottir and Maria Eriksdotter and Marianne Schultzberg and Erik Hjorth",

note = "Funding Information: The authors gratefully acknowledge the support given by the Swedish Alzheimer Foundation, the Swedish Research Council (2018-02601), Stockholm County Council (SLL20180425, RS 2019-1054), the Swedish Dementia Foundation, the China Scholarship Council (YW), the Foundation for Old Servants, the Foundation of Gun and Bertil Stohne and the {\AA}hl{\'e}n foundation. Publisher Copyright: {\textcopyright} 2021 Bentham Science Publishers.",

year = "2021",

doi = "10.2174/1567205018666210330162207",

language = "English",

volume = "18",

pages = "157--170",

journal = "Current Alzheimer Research",

issn = "1567-2050",

publisher = "Bentham Science Publishers B.V.",

number = "2",

}

TY - JOUR

T1 - Cerebrospinal fluid inflammatory markers in alzheimer’s disease

T2 - Influence of comorbidities

AU - Wang, Ying

AU - Emre, Ceren

AU - Gyllenhammar-Schill, Helena

AU - Fjellman, Karin

AU - Eyjolfsdottir, Helga

AU - Eriksdotter, Maria

AU - Schultzberg, Marianne

AU - Hjorth, Erik

N1 - Funding Information: The authors gratefully acknowledge the support given by the Swedish Alzheimer Foundation, the Swedish Research Council (2018-02601), Stockholm County Council (SLL20180425, RS 2019-1054), the Swedish Dementia Foundation, the China Scholarship Council (YW), the Foundation for Old Servants, the Foundation of Gun and Bertil Stohne and the Åhlén foundation. Publisher Copyright: © 2021 Bentham Science Publishers.

PY - 2021

Y1 - 2021

N2 - Background: Alzheimer's disease (AD) develops into dementia after several years, and subjective cognitive impairment (SCI) and mild cognitive impairment (MCI) are used as intermediary diagnoses of increasing severity. Inflammation is an important part of AD pathology and provides potential novel biomarkers and treatment targets. Objective: To identify novel potential biomarkers of AD in cerebrospinal fluid (CSF) and create a molecular pattern of inflammatory factors providing differentiation between AD and SCI. Methods: We analyzed 43 inflammatory-related mediators in CSF samples from a cohort of SCI and AD cases vetted for confounding factors (Training cohort). Using multivariate analysis (MVA), a model for discrimination between SCI and AD was produced, which we then applied to a larger non-vetted cohort (named Test cohort). The data were analyzed for factors showing differences between diagnostic groups and factors that differed between the vetted and non-vetted cohorts. The relationship of the factors to the agreement between model and clinical diagnosis was investigated. Results: A good MVA model able to discriminate AD from SCI without including tangle and plaque biomarkers was produced from the Training cohort. The model showed 50% agreement with clinical diagnosis in the Test cohort. Comparison of the cohorts indicated different patterns of factors distin-guishing SCI from AD. As an example, soluble interleukin (IL)-6Rα showed lower levels in AD cases in the Training cohort, whereas placental growth factor (PlGF) and serum amyloid A (SAA) levels were higher in AD cases of the Test cohort. The levels of p-tau were also higher in the Training cohort. Conclusion: This study provides new knowledge regarding the involvement of inflammation in AD by indicating different patterns of factors in CSF depending on whether potential confounding comorbid-ities are present or not, and presents sIL-6Rα as a potential new biomarker for improved diagnosis of AD.

AB - Background: Alzheimer's disease (AD) develops into dementia after several years, and subjective cognitive impairment (SCI) and mild cognitive impairment (MCI) are used as intermediary diagnoses of increasing severity. Inflammation is an important part of AD pathology and provides potential novel biomarkers and treatment targets. Objective: To identify novel potential biomarkers of AD in cerebrospinal fluid (CSF) and create a molecular pattern of inflammatory factors providing differentiation between AD and SCI. Methods: We analyzed 43 inflammatory-related mediators in CSF samples from a cohort of SCI and AD cases vetted for confounding factors (Training cohort). Using multivariate analysis (MVA), a model for discrimination between SCI and AD was produced, which we then applied to a larger non-vetted cohort (named Test cohort). The data were analyzed for factors showing differences between diagnostic groups and factors that differed between the vetted and non-vetted cohorts. The relationship of the factors to the agreement between model and clinical diagnosis was investigated. Results: A good MVA model able to discriminate AD from SCI without including tangle and plaque biomarkers was produced from the Training cohort. The model showed 50% agreement with clinical diagnosis in the Test cohort. Comparison of the cohorts indicated different patterns of factors distin-guishing SCI from AD. As an example, soluble interleukin (IL)-6Rα showed lower levels in AD cases in the Training cohort, whereas placental growth factor (PlGF) and serum amyloid A (SAA) levels were higher in AD cases of the Test cohort. The levels of p-tau were also higher in the Training cohort. Conclusion: This study provides new knowledge regarding the involvement of inflammation in AD by indicating different patterns of factors in CSF depending on whether potential confounding comorbid-ities are present or not, and presents sIL-6Rα as a potential new biomarker for improved diagnosis of AD.

KW - Alzheimer’s disease

KW - Biomarker

KW - Cerebrospinal fluid

KW - Diagnosis

KW - Inflammation

KW - Multivariate analysis

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U2 - 10.2174/1567205018666210330162207

DO - 10.2174/1567205018666210330162207

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AN - SCOPUS:85108304040

SN - 1567-2050

VL - 18

SP - 157

EP - 170

JO - Current Alzheimer Research

JF - Current Alzheimer Research

IS - 2

ER -

Cerebrospinal fluid inflammatory markers in alzheimer’s disease: Influence of comorbidities

Abstract

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