Associations of cerebrospinal fluid amyloidogenic nanoplaques with cytokines in Alzheimer’s disease
Abstract Background The aggregation of amyloid β (Aβ) is central in the pathogenesis of Alzheimer’s disease (AD). Recently it has been shown that specifically, larger, Thioflavin T-binding Aβ aggregates are associated with increased neuroinflammation and cytokine release. This study was aimed to qua...
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doaj-1249e7e2748045559a301e9f602c24992021-06-13T11:56:02ZengBMCTranslational Neurodegeneration2047-91582021-06-0110111010.1186/s40035-021-00244-3Associations of cerebrospinal fluid amyloidogenic nanoplaques with cytokines in Alzheimer’s diseaseMari Aksnes0Hans Christian D. Aass1Ann Tiiman2Trine Holt Edwin3Lars Terenius4Nenad Bogdanović5Vladana Vukojević6Anne-Brita Knapskog7Department of Geriatric Medicine, Institute of Clinical Medicine, Faculty of Medicine, University of OsloDepartment of Medical Biochemistry, Oslo University HospitalDepartment of Clinical Neurosciences (CNS), Center for Molecular Medicine CMM L8:01, Karolinska InstitutetDepartment of Geriatric Medicine, The Memory Clinic, Oslo University HospitalDepartment of Clinical Neurosciences (CNS), Center for Molecular Medicine CMM L8:01, Karolinska InstitutetDepartment of Neurobiology, Care Science and Society (NVS), Division of Clinical Geriatrics, Karolinska InstitutetDepartment of Clinical Neurosciences (CNS), Center for Molecular Medicine CMM L8:01, Karolinska InstitutetDepartment of Geriatric Medicine, The Memory Clinic, Oslo University HospitalAbstract Background The aggregation of amyloid β (Aβ) is central in the pathogenesis of Alzheimer’s disease (AD). Recently it has been shown that specifically, larger, Thioflavin T-binding Aβ aggregates are associated with increased neuroinflammation and cytokine release. This study was aimed to quantify fibrillary amyloid aggregates, so-called nanoplaques, and investigate their relationship with cytokines in the cerebrospinal fluid (CSF). Methods CSF was collected from 111 patients assessed for cognitive complaints at the Oslo University Hospital Memory Clinic. The patients were grouped based on their amyloid status. The CSF nanoplaque concentration was quantified with the Thioflavin T-fluorescence correlation spectroscopy (ThT-FCS) assay. The levels of nine cytokines (eotaxin-1, granulocyte stimulating factor, interleukin [IL]-6, IL-7, IL-8, monocyte chemoattractant protein-1, gamma-induced protein 10, macrophage inflammatory protein [MIP]-1α, and MIP-1β) were quantified with a magnetic bead-based multiplex assay and read on a Luminex IS 200 instrument. Results There were 49 amyloid-negative and 62 amyloid-positive patients in the cohort; none of the cytokines differed significantly between the amyloid groups. The increased nanoplaque levels were associated with levels of MIP-1β below the lower limit of quantification, and with decreased levels of MIP-1α and IL-8. The associations remained significant when adjusted for age, sex, cognitive function, apolipoprotein ε4 status and CSF core biomarker levels. Conclusion The cytokine levels were not associated with amyloid status in this cohort. The nanoplaque levels were negatively associated with MIP-1β, MIP-1α and IL-8, which is in line with recent findings suggesting that the upregulation of some cytokine markers has a protective role and is negatively associated with AD progression.https://doi.org/10.1186/s40035-021-00244-3Alzheimer's diseaseAmyloidAmyloid beta peptidesAmyloidogenic proteinsBiomarkersCerebrospinal fluid |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Mari Aksnes Hans Christian D. Aass Ann Tiiman Trine Holt Edwin Lars Terenius Nenad Bogdanović Vladana Vukojević Anne-Brita Knapskog |
spellingShingle |
Mari Aksnes Hans Christian D. Aass Ann Tiiman Trine Holt Edwin Lars Terenius Nenad Bogdanović Vladana Vukojević Anne-Brita Knapskog Associations of cerebrospinal fluid amyloidogenic nanoplaques with cytokines in Alzheimer’s disease Translational Neurodegeneration Alzheimer's disease Amyloid Amyloid beta peptides Amyloidogenic proteins Biomarkers Cerebrospinal fluid |
author_facet |
Mari Aksnes Hans Christian D. Aass Ann Tiiman Trine Holt Edwin Lars Terenius Nenad Bogdanović Vladana Vukojević Anne-Brita Knapskog |
author_sort |
Mari Aksnes |
title |
Associations of cerebrospinal fluid amyloidogenic nanoplaques with cytokines in Alzheimer’s disease |
title_short |
Associations of cerebrospinal fluid amyloidogenic nanoplaques with cytokines in Alzheimer’s disease |
title_full |
Associations of cerebrospinal fluid amyloidogenic nanoplaques with cytokines in Alzheimer’s disease |
title_fullStr |
Associations of cerebrospinal fluid amyloidogenic nanoplaques with cytokines in Alzheimer’s disease |
title_full_unstemmed |
Associations of cerebrospinal fluid amyloidogenic nanoplaques with cytokines in Alzheimer’s disease |
title_sort |
associations of cerebrospinal fluid amyloidogenic nanoplaques with cytokines in alzheimer’s disease |
publisher |
BMC |
series |
Translational Neurodegeneration |
issn |
2047-9158 |
publishDate |
2021-06-01 |
description |
Abstract Background The aggregation of amyloid β (Aβ) is central in the pathogenesis of Alzheimer’s disease (AD). Recently it has been shown that specifically, larger, Thioflavin T-binding Aβ aggregates are associated with increased neuroinflammation and cytokine release. This study was aimed to quantify fibrillary amyloid aggregates, so-called nanoplaques, and investigate their relationship with cytokines in the cerebrospinal fluid (CSF). Methods CSF was collected from 111 patients assessed for cognitive complaints at the Oslo University Hospital Memory Clinic. The patients were grouped based on their amyloid status. The CSF nanoplaque concentration was quantified with the Thioflavin T-fluorescence correlation spectroscopy (ThT-FCS) assay. The levels of nine cytokines (eotaxin-1, granulocyte stimulating factor, interleukin [IL]-6, IL-7, IL-8, monocyte chemoattractant protein-1, gamma-induced protein 10, macrophage inflammatory protein [MIP]-1α, and MIP-1β) were quantified with a magnetic bead-based multiplex assay and read on a Luminex IS 200 instrument. Results There were 49 amyloid-negative and 62 amyloid-positive patients in the cohort; none of the cytokines differed significantly between the amyloid groups. The increased nanoplaque levels were associated with levels of MIP-1β below the lower limit of quantification, and with decreased levels of MIP-1α and IL-8. The associations remained significant when adjusted for age, sex, cognitive function, apolipoprotein ε4 status and CSF core biomarker levels. Conclusion The cytokine levels were not associated with amyloid status in this cohort. The nanoplaque levels were negatively associated with MIP-1β, MIP-1α and IL-8, which is in line with recent findings suggesting that the upregulation of some cytokine markers has a protective role and is negatively associated with AD progression. |
topic |
Alzheimer's disease Amyloid Amyloid beta peptides Amyloidogenic proteins Biomarkers Cerebrospinal fluid |
url |
https://doi.org/10.1186/s40035-021-00244-3 |
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