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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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Advances in the development of new biomarkers for Alzheimer’s disease

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Translational Neurodegeneration 2022年第1期11卷 601-624页

作者： Timofey O.Klyucherev Pawel Olszewski Alena A.Shalimova Vladimir N.Chubarev Vadim V.Tarasov Misty M.Attwood Stina Syvänen Helgi B.Schiöth Department of Neuroscience Functional PharmacologyUniversity of Upp-salaUppsalaSweden Department of Pharmacology Institute of PharmacyI.M.Sechenov First Moscow State Medical UniversityMoscowRussia Institute of Translational Medicine and Biotechnology I.M.Sechenov First Moscow State Medical UniversityMoscowRussia Department of Public Health and Caring Sciences Rudbeck LaboratoryUppsala UniversityUppsalaSweden.

Alzheimer’s disease(AD)is a complex,heterogeneous,progressive disease and is the most common type of neurodegenerative *** prevalence of AD is expected to increase as the population ages,placing an additional burden on national healthcare *** is a large need for new diagnostic tests that can detect AD at an early stage with high specificity at relatively low *** development of modern analytical diagnostic tools has made it possible to determine several biomarkers of AD with high specificity,including pathogenic proteins,markers of synaptic dysfunction,and markers of inflammation in the *** is a considerable potential in using microRNA(miRNA)as markers of AD,and diagnostic studies based on miRNA panels suggest that AD could potentially be determined with high accuracy for individual *** of the retina with improved methods of visualization of the fundus are also showing promising results for the potential diagnosis of the *** review focuses on the recent developments of blood,plasma,and ocular biomarkers for the diagnosis of AD.

关键词： Alzheimer’s disease amyloid beta peptides Biomarkers Blood Cytokines Inflammation MicroRNA Ocular biomarkers

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Elevated plasma levels of soluble TNFRs and TACE activity in Alzheimer's disease patients in Han Chinese

Elevated plasma levels of soluble TNFRs and TACE activity in...

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中国神经科学学会第九届全国学术会议暨第五次会员代表大会

作者： Lin BAI~1,Ning SONG~1,Hua-Min XU~1,Jin-Tai YU~2,Lan TAN~2,Jun-Xia XIE~1,Hong JIANG~(1,*) 1 Department of Physiology,Shandong Provincial Key Laboratory of Pathogenesis and Prevention of Neurological Disorders and State Key Disciplines:Physiology,Medical College of Qingdao University,Qingdao 266071,China 2 Department of Neurology,Qingdao Municipal Hospital,Medical College of Qingdao University,Qingdao 266071, China

Objective Generation and deposition of amyloid beta peptides(AB) and neurofibrillary tangle formation are key mechanisms involved in Alzheimer’s disease(AD) *** is evidence supporting that tumor necrosis factor-α(TNF-α) receptors(TNFRs)-mediated signal pathway might contribute to production of AB and the subsequent cytotoxicity in the ***,the levels of soluble form of TNFRs(sTNFRs) and TNF-αconverting enzyme(TACE/ADAM-17) was not determined in AD *** In the present study,we analyzed sTNFRs levels and TACE activity in plasma at baseline in 76 patients of AD and 40 age- and sex-matched *** The AD patients had higher levels of both sTNFRs and TACE activity in plasma at baseline when compared with age-and sex-matched *** the subjects of AD,the sTNFRl levels correlated significantly to TACE activity(r = 0.385, P<0.01) and there were also positive and strong correlations between the sTNFRl and sTNFR2 in AD(r = 0.526,P<0.001).Conclusion These results suggest that sTNFRs and TACE might be involved in the neuropathogenesis of AD.

关键词： Alzheimer’s disease amyloid beta peptides soluble tumor necrosis factor receptor tumor necrosis factor converting enzyme

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