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

Translational Neurodegeneration 2021年第2期10卷 230-239页

作者： Mari Aksnes Hans Christian DAass ann tiiman Trine Holt Edwin Lars Terenius Nenad Bogdanovic Vladana Vukojevic anne-Brita Knapskog Department of Geriatric Medicine Institute of Clinical MedicineFaculty of MedicineUniversity of OsloOsloNorway Department of Medical Biochemistry Oslo University HospitalOsloNorway Department of Clinical Neurosciences(CNS) Center for Molecular Medicine CMM L8:01Karolinska InstitutetStockholmSweden Department of Geriatric Medicine The Memory ClinicOslo University HospitalOsloNorway Institute of Health and Society Faculty of MedicineUniversity of OsloOsloNorway Norwegian National Advisory Unit on Ageing and Health Vestfold Hospital TrustTonsbergNorway Department of Neurobiology Care Science and Society(NVS)Division of Clinical GeriatricsKarolinska InstitutetHuddingeSweden

Background:The aggregation of amyloidβ(Aβ)is central in the pathogenesis of Alzheimer’s disease(AD).Recently it has been shown that specifically,larger,Thioflavin T-binding Aβaggregates are associated with increased neuroinflammation and cytokine *** 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 *** patients were grouped based on their amyloid *** CSF nanoplaque concentration was quantified with the Thioflavin T-fluorescence correlation spectroscopy(ThT-FCS)*** levels of nine cytokines(eotaxin-1,granulocyte stimulating factor,interleukin[IL]-6,IL-7,IL-8,monocyte chemoattractant protein-1,gammainduced 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 ***:There were 49 amyloid-negative and 62 amyloid-positive patients in the cohort;none of the cytokines differed significantly between the amyloid *** increased nanoplaque levels were associated with levels of MIP-1βbelow the lower limit of quantification,and with decreased levels of MIP-1αand *** associations remained significant when adjusted for age,sex,cognitive function,apolipoproteinε4 status and CSF core biomarker ***:The cytokine levels were not associated with amyloid status in this *** nanoplaque levels were negatively associated with MIP-1β,MIP-1αand 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.

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

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