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Research paper
Different neuroinflammatory profile in amyotrophic lateral sclerosis and frontotemporal dementia is linked to the clinical phase
  1. Patrick Oeckl1,
  2. Patrick Weydt1,
  3. Petra Steinacker1,
  4. Sarah Anderl-Straub1,
  5. Frida Nordin2,
  6. Alexander E Volk3,
  7. Janine Diehl-Schmid4,
  8. Peter M Andersen1,2,
  9. Johannes Kornhuber5,
  10. Adrian Danek6,
  11. Klaus Fassbender7,
  12. Klaus Fliessbach8,
  13. German Consortium for Frontotemporal Lobar Degeneration9,
  14. Holger Jahn10,
  15. Martin Lauer11,
  16. Kathrin Müller1,
  17. Antje Knehr1,
  18. Johannes Prudlo12,
  19. Anja Schneider8,
  20. Dietmar R Thal13,14,
  21. Deniz Yilmazer-Hanke1,
  22. Jochen H Weishaupt1,
  23. Albert C Ludolph1,
  24. Markus Otto1
  1. 1 Department of Neurology, Ulm University Hospital, Ulm, Germany
  2. 2 Department of Pharmacology and Clinical Neurosciences, Umeå University, Umeå, Sweden
  3. 3 Institute of Human Genetics, University Medical Centre Hamburg-Eppendorf, Hamburg, Germany
  4. 4 Department of Psychiatry, Technical University of Munich, Munich, Germany
  5. 5 Department of Psychiatry, Friedrich-Alexander University Erlangen-Nuremberg, Erlangen, Germany
  6. 6 Department of Neurology, LMU Munich, Munich, Germany
  7. 7 Department of Neurology, Saarland University, Homburg, Germany
  8. 8 Department of Neurodegenerative Diseases and Geriatric Psychiatry, University of Bonn and DZNE Bonn, Bonn, Germany
  9. 9 German Consortium for Frontotemporal Lobar Degeneration, University of Ulm, Ulm, Germany
  10. 10 Department of Psychiatry, University Hospital Hamburg, Hamburg, Germany
  11. 11 Department of Psychiatry and Psychotherapy, University of Würzburg, Würzburg, Germany
  12. 12 Department of Neurology, University of Rostock, and German Center for Neurodegenerative Diseases (DZNE), Rostock, Germany
  13. 13 Department of Neuroscience, KU Leuven and Department of Pathology, UZ Leuven, Belgium
  14. 14 Laboratory of Neuropathology, Institute of Pathology, Ulm University, Ulm, Germany
  1. Correspondence to Markus Otto, Department of Neurology, Ulm University Hospital, Ulm D-89081, Germany; markus.otto{at}


Objective To investigate the role of neuroinflammation in asymptomatic and symptomatic amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD) mutation carriers.

Methods The neuroinflammatory markers chitotriosidase 1 (CHIT1), YKL-40 and glial fibrillary acidic protein (GFAP) were measured in cerebrospinal fluid (CSF) and blood samples from asymptomatic and symptomatic ALS/FTD mutation carriers, sporadic cases and controls by ELISA.

Results CSF levels of CHIT1, YKL-40 and GFAP were unaffected in asymptomatic mutation carriers (n=16). CHIT1 and YKL-40 were increased in gALS (p<0.001, n=65) whereas GFAP was not affected. Patients with ALS carrying a CHIT1 polymorphism had lower CHIT1 concentrations in CSF (−80%) whereas this polymorphism had no influence on disease severity. In gFTD (n=23), increased YKL-40 and GFAP were observed (p<0.05), whereas CHIT1 was nearly not affected. The same profile as in gALS and gFTD was observed in sALS (n=64/70) and sFTD (n=20/26). CSF and blood concentrations correlated moderately (CHIT1, r=0.51) to weak (YKL-40, r=0.30, GFAP, r=0.39). Blood concentrations of these three markers were not significantly altered in any of the groups except CHIT1 in gALS of the Ulm cohort (p<0.05).

Conclusion Our data indicate that neuroinflammation is linked to the symptomatic phase of ALS/FTD and shows a similar pattern in sporadic and genetic cases. ALS and FTD are characterised by a different neuroinflammatory profile, which might be one driver of the diverse presentations of the ALS/FTD syndrome.

  • neuroinflammation
  • amyotrophic lateral sclerosis
  • frontotemporal dementia
  • GFAP
  • cerebrospinal fluid
  • CHIT1

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  • Contributors Design or conceptualisation of the study: PO, PW, JHW, ACL, MO. Analysis or interpretation of data: PO, PW, PS, SAS, FN, AEV, JDS, PMA, HJ, JK, AD, KFa, KFl, ML, KM, AK, JP, AS, DRT, DYH, JHW, ACL, MO. Drafting or revising the manuscript for intellectual content: PO, PW, PS, SAS, FN, AEV, JDS, PMA, HJ, JK, AD, KFa, KFl, ML, KM, AK, JP, AS, DRT, DYH, JHW, ACL, MO.

  • Funding This study was supported by the EU Joint Programme–Neurodegenerative Disease Research (JPND) networks SOPHIA (01ED1202A), BiomarkAPD (01ED1203F), and PreFrontAls (01ED1512), the German Federal Ministry of Education and Research (FTLDcO1GI1007A, MND-Net 01GM1103A), the EU (NADINE 246513, FAIR-PARK II 633190,STRENTH/JPND), the German Research Foundation/DFG (VO2028, SFB1279), the foundation of the state Baden-Württemberg (D3830), Boehringer Ingelheim Ulm University BioCenter (D5009), Thierry Latran Foundation, Departmental Funds (GPS-ALS Study), the Charcot Foundation, the Swedish Brain Research Foundation, the Bertil Hållsten Foundation, the Swedish Research Council, the Knut and Alice Wallenberg Foundation, and the Ulla-Carin Lindquist Foundation.

  • Disclaimer The funders were not involved in the study design, in the collection, analysis and interpretation of data, in the writing of the report; and in the decision to submit the paper for publication.

  • Competing interests DRT received consultancies from Covance Laboratories (UK) and GE Healthcare (UK), received a speaker honorarium from GE Healthcare (UK), and collaborated with Novartis Pharma Basel (Switzerland).

    PO, PW, PS, SAS, FN, AEV, JDS, PMA, JK, AD, KFa, KFl, HJ, ML, KM, AK, JP, AS, DYH, JHW, ACL and MO report no competing interests.

  • Patient consent Not required

  • Ethics approval Ethics committees of the Universities of Ulm, Umea, Munich, Erlangen, Homburg, Bonn. The Medical Ethical Review Boards of the participating centers approved the study.

  • Provenance and peer review Not commissioned; externally peer reviewed.

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