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Title: | Elevated CSF and plasma complement proteins in genetic frontotemporal dementia: results from the GENFI study |
Author: | Ende, Emma L. van der Heller, Carolin Sogorb Esteve, Aitana Swift, Imogen J. McFall, David Peakman, Georgia Bouzigues, Arabella Poos, Jackie M. Jiskoot, Lize C. Panman, Jessica L. Papma, Janne M. Meeter, Lieke H. Dopper, Elise G. P. Bocchetta, Martina Todd, Emily Cash, David Graff, Caroline Synofzik, Matthis Moreno, Fermin Finger, Elizabeth Sánchez Valle, Raquel Vandenberghe, Rik Laforce, Robert Masellis, Mario Tartaglia, Maria Carmela Rowe, James B. Butler, Chris Ducharme, Simon Gerhard, Alexander Danek, Adrian Levin, Johannes Pijnenburg, Yolande A. L. Otto, Markus Borroni, Barbara Tagliavini, Fabrizio Mendonça, Alexandre de Santana, Isabel Galimberti, Daniela Sorbi, Sandro Zetterberg, Henrik |
Keywords: | Demència Demència Marcadors bioquímics Dementia Dementia Biochemical markers |
Issue Date: | 5-Sep-2022 |
Publisher: | Springer Nature |
Abstract: | Neuroinflammation is emerging as an important pathological process in frontotemporal dementia (FTD), but biomarkers are lacking. We aimed to determine the value of complement proteins, which are key components of innate immunity, as biomarkers in cerebrospinal fluid (CSF) and plasma of presymptomatic and symptomatic genetic FTD mutation carriers.We measured the complement proteins C1q and C3b in CSF by ELISAs in 224 presymptomatic and symptomatic GRN, C9orf72 or MAPT mutation carriers and non-carriers participating in the Genetic Frontotemporal Dementia Initiative (GENFI), a multicentre cohort study. Next, we used multiplex immunoassays to measure a panel of 14 complement proteins in plasma of 431 GENFI participants. We correlated complement protein levels with corresponding clinical and neuroimaging data, neurofilament light chain (NfL) and glial fibrillary acidic protein (GFAP).CSF C1q and C3b, as well as plasma C2 and C3, were elevated in symptomatic mutation carriers compared to presymptomatic carriers and non-carriers. In genetic subgroup analyses, these differences remained statistically significant for C9orf72 mutation carriers. In presymptomatic carriers, several complement proteins correlated negatively with grey matter volume of FTD-related regions and positively with NfL and GFAP. In symptomatic carriers, correlations were additionally observed with disease duration and with Mini Mental State Examination and Clinical Dementia Rating scale® plus NACC Frontotemporal lobar degeneration sum of boxes scores.Elevated levels of CSF C1q and C3b, as well as plasma C2 and C3, demonstrate the presence of complement activation in the symptomatic stage of genetic FTD. Intriguingly, correlations with several disease measures in presymptomatic carriers suggest that complement protein levels might increase before symptom onset. Although the overlap between groups precludes their use as diagnostic markers, further research is needed to determine their potential to monitor dysregulation of the complement system in FTD.© 2022. The Author(s). |
Note: | Reproducció del document publicat a: https://doi.org/10.1186/s12974-022-02573-0 |
It is part of: | Journal Of Neuroinflammation, 2022, vol. 19, num. 1 |
URI: | http://hdl.handle.net/2445/206702 |
Related resource: | https://doi.org/10.1186/s12974-022-02573-0 |
ISSN: | 1742-2094 |
Appears in Collections: | Articles publicats en revistes (IDIBAPS: Institut d'investigacions Biomèdiques August Pi i Sunyer) |
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