Associations of cerebrospinal fluid amyloidogenic nanoplaques with cytokines in Alzheimer’s disease

Translational Neurodegeneration

Vladana Vukojević¹  Ann Tiiman¹  Lars Terenius¹  Mari Aksnes²  Anne-Brita Knapskog³  Trine Holt Edwin⁴  Hans Christian D. Aass⁵  Nenad Bogdanović⁶ 

[1] Department of Clinical Neurosciences (CNS), Center for Molecular Medicine CMM L8:01, Karolinska Institutet, Stockholm, Sweden;Department of Geriatric Medicine, Institute of Clinical Medicine, Faculty of Medicine, University of Oslo, Oslo, Norway;Department of Geriatric Medicine, The Memory Clinic, Oslo University Hospital, Oslo, Norway;Department of Geriatric Medicine, The Memory Clinic, Oslo University Hospital, Oslo, Norway;Institute of Health and Society, Faculty of Medicine, University of Oslo, Oslo, Norway;Norwegian National Advisory Unit on Ageing and Health, Vestfold Hospital Trust, Tønsberg, Norway;Department of Medical Biochemistry, Oslo University Hospital, Oslo, Norway;Department of Neurobiology, Care Science and Society (NVS), Division of Clinical Geriatrics, Karolinska Institutet, Huddinge, Sweden;

关键词: Alzheimer's disease;    Amyloid;    Amyloid beta peptides;    Amyloidogenic proteins;    Biomarkers;    Cerebrospinal fluid;    Cytokines;    Inflammation;    Fluorescence correlation spectroscopy;    Thioflavin T;   

DOI  :  10.1186/s40035-021-00244-3

来源: Springer

【 摘 要 】

BackgroundThe 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).MethodsCSF 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.ResultsThere 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.ConclusionThe 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.

【 授权许可】

CC BY