Evidence map›Paper›PMID 36064709›Full record

ArticleJournal of neuroinflammation2022

Elevated CSF and plasma complement proteins in genetic frontotemporal dementia: results from the GENFI study.

Emma L van der Ende, Carolin Heller, Aitana Sogorb-Esteve, Imogen J Swift, David McFall, Georgia Peakman, Arabella Bouzigues, Jackie M Poos, Lize C Jiskoot, Jessica L Panman and 35 more

Open access · goldAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Journal of neuroinflammation, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 26 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
26citing papers in PubMed, 1 pooled it
2.8field-weighted citation impact, top 8% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

26 citing papers in PubMed, 1 synthesis or guideline pooled it, 35 citations in OpenAlex.

  1. Pooled it
  2. Article
  3. Review
  4. Proteomic biomarkers of cognitive function,medRxiv : the preprint server for health sciences · 2026
    Article
  5. Review
  6. Review
  7. Article
  8. Review
  9. Article
  10. Article
  11. Review
  12. Article
  13. Review
  14. Article
  15. Article
  16. Review
  17. Article
  18. Article
  19. Review
  20. The complement system in neurodegenerative diseases.Clinical science (London, England : 1979) · 2024
    Article
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

45 authors at 20 institutions in 10 countries.

Emma L van der Ende *Alzheimer Center Rotterdam and Department of Neurology, Erasmus University Medical Center, PO Box 2040, 3000 CA, Rotterdam, The Netherlands.
Carolin Heller *UK Dementia Research Institute at University College London, UCL Queen Square Institute of Neurology, London, UK.
Aitana Sogorb-EsteveUK Dementia Research Institute at University College London, UCL Queen Square Institute of Neurology, London, UK.
Imogen J SwiftUK Dementia Research Institute at University College London, UCL Queen Square Institute of Neurology, London, UK.
David McFallDepartment of Pathology, University of California San Francisco, San Francisco, USA.
Georgia PeakmanDementia Research Centre, Department of Neurodegenerative Disease, UCL Queen Square Institute of Neurology, University College London, London, UK.
Arabella BouziguesDementia Research Centre, Department of Neurodegenerative Disease, UCL Queen Square Institute of Neurology, University College London, London, UK.
Jackie M PoosAlzheimer Center Rotterdam and Department of Neurology, Erasmus University Medical Center, PO Box 2040, 3000 CA, Rotterdam, The Netherlands.
Lize C JiskootAlzheimer Center Rotterdam and Department of Neurology, Erasmus University Medical Center, PO Box 2040, 3000 CA, Rotterdam, The Netherlands.
Jessica L PanmanAlzheimer Center Rotterdam and Department of Neurology, Erasmus University Medical Center, PO Box 2040, 3000 CA, Rotterdam, The Netherlands.
Janne M PapmaAlzheimer Center Rotterdam and Department of Neurology, Erasmus University Medical Center, PO Box 2040, 3000 CA, Rotterdam, The Netherlands.
Lieke H MeeterAlzheimer Center Rotterdam and Department of Neurology, Erasmus University Medical Center, PO Box 2040, 3000 CA, Rotterdam, The Netherlands.
Elise G P DopperAlzheimer Center Rotterdam and Department of Neurology, Erasmus University Medical Center, PO Box 2040, 3000 CA, Rotterdam, The Netherlands.
Martina BocchettaDementia Research Centre, Department of Neurodegenerative Disease, UCL Queen Square Institute of Neurology, University College London, London, UK.
Emily ToddDementia Research Centre, Department of Neurodegenerative Disease, UCL Queen Square Institute of Neurology, University College London, London, UK.
David CashDementia Research Centre, Department of Neurodegenerative Disease, UCL Queen Square Institute of Neurology, University College London, London, UK.
Caroline GraffCenter for Alzheimer Research, Division of Neurogeriatrics, Department of Neurobiology, Care Sciences and Society, Bioclinicum, Karolinska Institutet, Solna, Sweden.
Matthis SynofzikGerman Center for Neurodegenerative Diseases (DZNE), Tübingen, Germany.
Fermin MorenoCognitive Disorders Unit, Department of Neurology, Hospital Universitario Donostia, San Sebastian, Gipuzkoa, Spain.
Elizabeth FingerDepartment of Clinical Neurological Sciences, University of Western Ontario, London, ON, Canada.
Raquel Sanchez-ValleAlzheimer's Disease and Other Cognitive Disorders Unit, Neurology Service, Hospital Clinic, IDIBAPS, University of Barcelona, Barcelona, Spain.
Rik VandenbergheLaboratory for Cognitive Neurology, Department of Neurosciences, Leuven Brain Institute, KU Leuven, Louvain, Belgium.
Robert LaforceClinique Interdisciplinaire de Mémoire, Département Des Sciences Neurologiques, CHU de Québec, Université Laval, Québec, Canada.
Mario MasellisSunnybrook Research Institute, Toronto, ON, Canada.
Maria Carmela TartagliaTanz Centre for Research in Neurodegenerative Disease, University of Toronto, Toronto, ON, Canada.
James B RoweCambridge University Centre for Frontotemporal Dementia, University of Cambridge, Cambridge, UK.
Chris ButlerNuffield Department of Clinical Neurosciences, Medical Sciences Division, University of Oxford, Oxford, UK.
Simon DucharmeMcConnell Brain Imaging Centre, Montreal Neurological Institute and McGill University Health Centre, McGill University, Montreal, Québec, Canada.
Alexander GerhardDepartment of Nuclear Medicine and Geriatric Medicine, University Hospital Essen, Essen, Germany.
Adrian DanekNeurologische Klinik Und Poliklinik, Ludwig-Maximilians-Universität München, Munich, Germany.
Johannes LevinNeurologische Klinik Und Poliklinik, Ludwig-Maximilians-Universität München, Munich, Germany.
Yolande A L PijnenburgAlzheimer Center Amsterdam, Department of Neurology, Amsterdam Neuroscience, Vrije Universiteit Amsterdam, Amsterdam UMC, Amsterdam, The Netherlands.
Markus OttoDepartment of Neurology, Universität Ulm, Ulm, Germany.
Barbara BorroniCentre for Neurodegenerative Disorders, Department of Clinical and Experimental Sciences, University of Brescia, Brescia, Italy.
Fabrizio TagliaviniFondazione IRCCS Istituto Neurologico Carlo Besta, Milan, Italy.
Alexandre de MendonçaFaculdade de Medicina da Universidade de Lisboa, Lisbon, Portugal.
Isabel SantanaCenter for Neuroscience and Cell Biology, Faculty of Medicine, University of Coimbra, Coimbra, Portugal.
Daniela GalimbertiFondazione IRCCS, Ospedale Maggiore Policlinico, Neurodegenerative Diseases Unit, Milan, Italy.
Sandro SorbiDepartment of Neurofarba, University of Florence, Florence, Italy.
Henrik ZetterbergUK Dementia Research Institute at University College London, UCL Queen Square Institute of Neurology, London, UK.
Eric HuangDepartment of Pathology, University of California San Francisco, San Francisco, USA.
John C van SwietenAlzheimer Center Rotterdam and Department of Neurology, Erasmus University Medical Center, PO Box 2040, 3000 CA, Rotterdam, The Netherlands.
Jonathan D Rohrer *Dementia Research Centre, Department of Neurodegenerative Disease, UCL Queen Square Institute of Neurology, University College London, London, UK.
Harro Seelaar *Alzheimer Center Rotterdam and Department of Neurology, Erasmus University Medical Center, PO Box 2040, 3000 CA, Rotterdam, The Netherlands. h.seelaar@erasmusmc.nl.
Genetic Frontotemporal Dementia Initiative (GENFI)
UK Dementia Research Institute · GBErasmus MC · NLUniversity of California, San Francisco · USUniversity of Coimbra · PTGerman Center for Neurodegenerative Diseases · DEKarolinska University Hospital · SEMontreal Neurological Institute and Hospital · CAUniversity of Brescia · ITAmsterdam Neuroscience · NLBiogipuzkoa Health Research Institute · ESConsorci Institut D'Investigacions Biomediques August Pi I Sunyer · ESFondazione IRCCS Istituto Neurologico Carlo Besta · ITKU Leuven · BELudwig-Maximilians-Universität München · DESunnybrook Hospital · CAUniversität Ulm · DEUniversité Laval · CAUniversity of Cambridge · GBUniversity of Florence · ITUniversity of Lisbon · PT

Funding

Alzheimer Nederland 733050813, 733050103, 733050513Deutsche Forschungsgemeinschaft 390857198EU Joint Programme - Neurodegenerative Disease Research 2019-02248EU Joint Programme - Neurodegenerative Disease Research 733051042, 733051024fundacio marato de TV3 20143810Horizon 2020 Framework Programme 779357Medical Research Council MC_UU_00024/1Medical Research Council MR/M008525/1Medical Research Council MR/M023664/1Medical Research Council MR/T046015/1NIHR Rare Disease Translational Research Collaboration BRC149/NS/MHStichting Dioraphte 14021300Vetenskapsrådet 529-2014-7504Wellcome TrustWellcome Trust 103838ZonMw 733050813, 733050103, 733050513
6 · The paper itself

Abstract

backgroundNeuroinflammation 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.

methodsWe 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).

resultsCSF 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.

conclusionsElevated 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.

Indexed as

Frontotemporal DementiaPick Disease of the BrainBiomarkersC9orf72 ProteinCohort StudiesComplement C1qComplement System ProteinsHumansBiomarkersC9orf72 ProteinComplement C1qComplement System ProteinsBiomarkerComplementFrontotemporal dementiaNeuroinflammation

Identifiers

PMID36064709
PMCPMC9446850
OpenAlexW4294647492

What OpenQuestion holds

Textmetadata
LicenceCC BY
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.