Inflammatory plasma profile in genetic symptomatic and presymptomatic Frontotemporal Dementia - A GENFI study.

Autor: Fenoglio C; Dept. of Biomedical, Surgical and Dental Sciences, University of Milan, Milan, Italy; Fondazione Ca' Granda, IRCCS Ospedale Maggiore Policlinico, Milan, Italy., Serpente M; Fondazione Ca' Granda, IRCCS Ospedale Maggiore Policlinico, Milan, Italy., Arcaro M; Fondazione Ca' Granda, IRCCS Ospedale Maggiore Policlinico, Milan, Italy., Carandini T; Fondazione Ca' Granda, IRCCS Ospedale Maggiore Policlinico, Milan, Italy., Sacchi L; Dept. of Biomedical, Surgical and Dental Sciences, University of Milan, Milan, Italy; Fondazione Ca' Granda, IRCCS Ospedale Maggiore Policlinico, Milan, Italy., Pintus M; Dept. of Biomedical, Surgical and Dental Sciences, University of Milan, Milan, Italy; Fondazione Ca' Granda, IRCCS Ospedale Maggiore Policlinico, Milan, Italy., Rotondo E; Fondazione Ca' Granda, IRCCS Ospedale Maggiore Policlinico, Milan, Italy., Borracci V; Fondazione Ca' Granda, IRCCS Ospedale Maggiore Policlinico, Milan, Italy., Ghezzi L; Dept. of Biomedical, Surgical and Dental Sciences, University of Milan, Milan, Italy; Fondazione Ca' Granda, IRCCS Ospedale Maggiore Policlinico, Milan, Italy., Bouzigues A; Dementia Research Centre, Department of Neurodegenerative Disease, UCL Queen Square Institute of Neurology, London, UK., Russell LL; Dementia Research Centre, Department of Neurodegenerative Disease, UCL Queen Square Institute of Neurology, London, UK., Foster PH; Dementia Research Centre, Department of Neurodegenerative Disease, UCL Queen Square Institute of Neurology, London, UK., Ferry-Bolder E; Dementia Research Centre, Department of Neurodegenerative Disease, UCL Queen Square Institute of Neurology, London, UK., van Swieten JC; Department of Neurology, Erasmus Medical Centre, Rotterdam, Netherlands., Jiskoot LC; Department of Neurology, Erasmus Medical Centre, Rotterdam, Netherlands., Seelaar H; Department of Neurology, Erasmus Medical Centre, Rotterdam, Netherlands., Sánchez Valle R; Alzheimer's Disease and Other Cognitive Disorders Unit, Neurology Service, Hospital Clínic de Barcelona, Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Fundació Clínic per a la Recerca Biomèdica, Universitat de Barcelona, Barcelona, Spain., Laforce R; Clinique Interdisciplinaire de Mémoire, Département des Sciences Neurologiques, CHU de Québec, and Faculté de Médecine, Université Laval, QC, Canada., Graff C; Department of Neurobiology, Care Sciences and Society, Center for Alzheimer Research, Division of Neurogeriatrics, Bioclinicum, Karolinska Institutet, Solna, Sweden; Unit for Hereditary Dementias, Theme Inflammation and Aging, Karolinska University Hospital, Solna, Sweden., Vandenberghe R; Laboratory for Cognitive Neurology, Department of Neurosciences, KU Leuven, Leuven, Belgium; Neurology Service, University Hospitals Leuven, Leuven, Belgium; Leuven Brain Institute, KU Leuven, Leuven, Belgium., de Mendonça A; Faculty of Medicine, University of Lisbon, Lisbon, Portugal., Tiraboschi P; Fondazione IRCCS Istituto Neurologico Carlo Besta, Milano, Italy., Santana I; University Hospital of Coimbra (HUC), Neurology Service, Faculty of Medicine, University of Coimbra, Coimbra, Portugal; Center for Neuroscience and Cell Biology, Faculty of Medicine, University of Coimbra, Coimbra, Portugal., Gerhard A; Division of Psychology Communication and Human Neuroscience, Wolfson Molecular Imaging Centre, University of Manchester, Manchester, UK; Department of Nuclear Medicine, Center for Translational Neuro- and Behavioral Sciences, University Medicine Essen, Essen, Germany; Department of Geriatric Medicine, Klinikum Hochsauerland, Arnsberg, Germany., Levin J; Department of Neurology, Ludwig-Maximilians Universität München, Munich, Germany; German Center for Neurodegenerative Diseases (DZNE), Munich, Germany; Munich Cluster of Systems Neurology (SyNergy), Munich, Germany., Sorbi S; Department of Neurofarba, University of Florence, Italy; IRCCS Fondazione Don Carlo Gnocchi, Florence, Italy., Otto M; Department of Neurology, University of Ulm, Germany., Pasquier F; University of Lille, France; Inserm 1172, Lille, France; CHU, CNR-MAJ, Labex Distalz, LiCEND Lille, France., Ducharme S; Department of Psychiatry, Douglas Mental Health University Institute, McGill University, Montreal, Québec, Canada; McConnell Brain Imaging Centre, Montreal Neurological Institute, McGill University, Montreal, Québec, Canada., Butler CR; Nuffield Department of Clinical Neurosciences, Medical Sciences Division, University of Oxford, Oxford, UK; Department of Brain Sciences, Imperial College London, UK., Ber IL; Sorbonne Université, Paris Brain Institute - Institut du Cerveau - ICM, Inserm U1127, CNRS UMR 7225, AP-HP - Hôpital Pitié-Salpêtrière, Paris, France; Centre de référence des démences rares ou précoces, IM2A, Département de Neurologie, AP-HP - Hôpital Pitié-Salpêtrière, Paris, France; Département de Neurologie, AP-HP - Hôpital Pitié-Salpêtrière, Paris, France., Finger E; Department of Clinical Neurological Sciences, University of Western Ontario, London, ON, Canada., Carmela Tartaglia M; Tanz Centre for Research in Neurodegenerative Diseases, University of Toronto, Toronto, ON, Canada., Masellis M; Sunnybrook Health Sciences Centre, Sunnybrook Research Institute, University of Toronto, Toronto, Canada., Rowe JB; Department of Clinical Neurosciences and Cambridge University Hospitals NHS Trust, University of Cambridge, UK., Synofzik M; Department of Neurodegenerative Diseases, Hertie-Institute for Clinical Brain Research and Center of Neurology, University of Tübingen, Tübingen, Germany; Center for Neurodegenerative Diseases (DZNE), Tübingen, Germany., Moreno F; Cognitive Disorders Unit, Department of Neurology, Donostia Universitary Hospital, San Sebastian, Spain; Biogipuzkoa Health Research Institute, Neurosciences Area, Group of Neurodegenerative Diseases, 20014 San Sebastian, Spain; Center for Biomedical Research in Neurodegenerative Disease (CIBERNED), Carlos III Health Institute, Madrid, Spain., Borroni B; Neurology Unit, Department of Clinical and Experimental Sciences, University of Brescia, Brescia, Italy., Rohrer JD; Dementia Research Centre, Department of Neurodegenerative Disease, UCL Queen Square Institute of Neurology, London, UK., Arighi A; Fondazione Ca' Granda, IRCCS Ospedale Maggiore Policlinico, Milan, Italy., Galimberti D; Dept. of Biomedical, Surgical and Dental Sciences, University of Milan, Milan, Italy; Fondazione Ca' Granda, IRCCS Ospedale Maggiore Policlinico, Milan, Italy. Electronic address: daniela.galimberti@unimi.it.
Jazyk: angličtina
Zdroj: Brain, behavior, and immunity [Brain Behav Immun] 2024 Nov; Vol. 122, pp. 231-240. Date of Electronic Publication: 2024 Aug 15.
DOI: 10.1016/j.bbi.2024.08.030
Abstrakt: Background: Inflammation has been proposed as a crucial player in neurodegeneration, including Frontotemporal Dementia (FTD). A few studies on sporadic FTD lead to inconclusive results, whereas large studies on genetic FTD are lacking. The aim of this study is to determine cytokine and chemokine plasma circulating levels in a large cohort of genetic FTD, collected within the GENetic Frontotemporal dementia Initiative (GENFI).
Methods: Mesoscale technology was used to analyse levels of 30 inflammatory factors in 434 plasma samples, including 94 Symptomatic Mutation carriers [(SMC); 15 with mutations in Microtubule Associated Protein Tau (MAPT) 34 in Progranulin (GRN) and 45 in Chromosome 9 Open Reading Frame (C9ORF)72], 168 Presymptomatic Mutation Carriers (PMC; 34 MAPT, 70 GRN and 64 C9ORF72) and 173 Non-carrier Controls (NC)].
Results: The following cytokines were significantly upregulated (P<0.05) in MAPT and GRN SMC versus NC: Tumor Necrosis Factor (TNF)α, Interleukin (IL)-7, IL-15, IL-16, IL-17A. Moreover, only in GRN SMC, additional factors were upregulated, including: IL-1β, IL-6, IL-10, IL-12/IL-23p40, eotaxin, eotaxin-3, Interferon γ-induced Protein (IP-10), Monocyte Chemotactic Protein (MCP)4. On the contrary, IL-1α levels were decreased in SMC compared with NC. Significantly decreased levels of this cytokine were also found in PMC, independent of the type of mutation. In SMC, no correlations between disease duration and cytokine and chemokine levels were found. Considering NfL and GFAP levels, as expected, significant increases were observed in SMC as compared to NC. These differences in mean values remain significant even when stratifying symptomatic patients by the mutated gene (P<0.0001). Considering instead the levels of NfL, GFAP, and the altered inflammatory molecules, no significant correlations emerged.
Conclusion: We showed that inflammatory proteins are upregulated in MAPT and GRN SMC, with some specific factors altered in GRN only, whereas no changes were seen in C9ORF72 carriers. Notably, only IL-1α levels were decreased in both SMC and PMC, independent of the type of causal mutation, suggesting common modifications occurring in the preclinical phase of the disease.
Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.
(Copyright © 2024 Elsevier Inc. All rights reserved.)
Databáze: MEDLINE
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