Different neuroinflammatory profile in amyotrophic lateral sclerosis and frontotemporal dementia is linked to the clinical phase
Open accessAbstract
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.
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Other studies observed no increase in blood GFAP in participants with FTD compared to controls.
“Indeed, some studies reported elevated blood GFAP in participants with FTD compared to controls [8–18] but others observed no such GFAP increase in FTD [19–22].”
From Comprehensive cross-sectional and longitudinal comparisons of plasma glial fibrillary acidic protein and neurofilament light across FTD spectrum disorders (2025) · cites this paper as [19]
Cites
Converging Mechanisms in ALS and FTD: Disrupted RNA and Protein Homeostasis
Ling, S.-C., Polymenidou, M., & Cleveland, D. W. (2013) · Neuron · doi:10.1016/j.neuron.2013.07.033 · Cited by 1,811 · see citing works
Onset and Progression in Inherited ALS Determined by Motor Neurons and Microglia
Boillée, S., Yamanaka, K., Lobsiger, C. S., Copeland, N. G., Jenkins, N. A., Kassiotis, G., Kollias, G., & Cleveland, D. W. (2006) · Science · doi:10.1126/science.1123511 · Cited by 1,623 · see citing works
Haploinsufficiency of TBK1 causes familial ALS and fronto-temporal dementia
Freischmidt, A., Wieland, T., Richter, B., Ruf, W., Schaeffer, V., Müller, K., Marroquin, N., Nordin, F., Hübers, A., Weydt, P., et al. (2015) · Nature Neuroscience · doi:10.1038/nn.4000 · Cited by 786 · see citing works
Self-citationTurner, M. R., Cagnin, A., Turkheimer, F. E., Miller, C. C. J., Shaw, C. E., Brooks, D. J., Leigh, P. N., & Banati, R. B. (2004) · Neurobiology of Disease · doi:10.1016/j.nbd.2003.12.012 · Cited by 737 · see citing works
ALS clinical trials review: 20 years of failure. Are we any closer to registering a new treatment?
Petrov, D., Mansfield, C., Moussy, A., & Hermine, O. (2017) · Frontiers in Aging Neuroscience · doi:10.3389/fnagi.2017.00068 · Cited by 451 · see citing works
Brettschneider, J., Toledo, J. B., Van Deerlin, V. M., Elman, L., McCluskey, L., Lee, V. M.-Y., & Trojanowski, J. Q. (2012) · PLoS ONE · doi:10.1371/journal.pone.0039216 · Cited by 268 · see citing works
Microglia and C9orf72 in neuroinflammation and ALS and frontotemporal dementia
Lall, D., & Baloh, R. H. (2017) · Journal of Clinical Investigation · doi:10.1172/jci90607 · Cited by 175 · see citing works
Ishiki, A., Kamada, M., Kawamura, Y., Terao, C., Shimoda, F., Tomita, N., Arai, H., & Furukawa, K. (2016) · Journal of Neurochemistry · doi:10.1111/jnc.13399 · Cited by 156 · see citing works
Cerebrospinal fluid macrophage biomarkers in amyotrophic lateral sclerosis
Thompson, A. G., Gray, E., Thézénas, M., Charles, P. D., Evetts, S., Hu, M. T., Talbot, K., Fischer, R., Kessler, B. M., & Turner, M. R. (2018) · Annals of Neurology · doi:10.1002/ana.25143 · Cited by 130 · see citing works
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An update on genetic frontotemporal dementia
Greaves, C. V., & Rohrer, J. D. (2019) · Journal of Neurology · doi:10.1007/s00415-019-09363-4 · Cited by 500 · see citing works
Plasma glial fibrillary acidic protein is raised in progranulin-associated frontotemporal dementia
Heller, C., Foiani, M. S., Moore, K., Convery, R., Bocchetta, M., Neason, M., Cash, D. M., Thomas, D., Greaves, C. V., Woollacott, I. O., et al. (2020) · Journal of Neurology, Neurosurgery & Psychiatry · doi:10.1136/jnnp-2019-321954 · Cited by 182 · see citing works
Self-citationFluid biomarkers in frontotemporal dementia: past, present and future
Swift, I. J., Sogorb-Esteve, A., Heller, C., Synofzik, M., Otto, M., Graff, C., Galimberti, D., Todd, E., Heslegrave, A. J., van der Ende, E. L., et al. (2021) · Journal of Neurology, Neurosurgery & Psychiatry · doi:10.1136/jnnp-2020-323520 · Cited by 122 · see citing works
Self-citationBéland, L.-C., Markovinovic, A., Jakovac, H., De Marchi, F., Bilic, E., Mazzini, L., Kriz, J., & Munitic, I. (2020) · Brain Communications · doi:10.1093/braincomms/fcaa124 · Cited by 125 · see citing works
Benussi, A., Ashton, N. J., Karikari, T. K., Gazzina, S., Premi, E., Benussi, L., Ghidoni, R., Rodriguez, J. L., Emeršič, A., Binetti, G., et al. (2020) · Journal of Alzheimer’s Disease · doi:10.3233/jad-200608 · Cited by 113 · see citing works
Oeckl, P., Anderl-Straub, S., Von Arnim, C. A. F., Baldeiras, I., Diehl-Schmid, J., Grimmer, T., Halbgebauer, S., Kort, A. M., Lima, M., Marques, T. M., et al. (2022) · Journal of Neurology, Neurosurgery & Psychiatry · doi:10.1136/jnnp-2021-328547 · Cited by 94 · see citing works
Self-citationZhu, N., Santos-Santos, M., Illán-Gala, I., Montal, V., Estellés, T., Barroeta, I., Altuna, M., Arranz, J., Muñoz, L., Belbin, O., et al. (2021) · Translational Neurodegeneration · doi:10.1186/s40035-021-00275-w · Cited by 86 · see citing works
Gut microbiota in ALS: possible role in pathogenesis?
McCombe, P. A., Henderson, R. D., Lee, A., Lee, J. D., Woodruff, T. M., Restuadi, R., McRae, A., Wray, N. R., Ngo, S., & Steyn, F. J. (2019) · Expert Review of Neurotherapeutics · doi:10.1080/14737175.2019.1623026 · Cited by 46 · see citing works
Barschke, P., Oeckl, P., Steinacker, P., Al Shweiki, M. R., Weishaupt, J. H., Landwehrmeyer, G. B., Anderl-Straub, S., Weydt, P., Diehl-Schmid, J., Danek, A., et al. (2020) · Journal of Neurology, Neurosurgery & Psychiatry · doi:10.1136/jnnp-2019-322476 · Cited by 45 · see citing works
Self-citationChu, M., Wen, L., Jiang, D., Liu, L., Nan, H., Yue, A., Wang, Y., Wang, Y., Qu, M., Wang, N., et al. (2023) · Journal of Neuroinflammation · doi:10.1186/s12974-023-02746-5 · Cited by 33 · see citing works
Sheth, U., Öijerstedt, L., Heckman, M. G., White, L. J., Heuer, H. W., Lario Lago, A., Forsberg, L. K., Faber, K. M., Foroud, T. M., Rademakers, R., et al. (2025) · Molecular Neurodegeneration · doi:10.1186/s13024-025-00821-4 · Cited by 20 · see citing works
The role of neurofilament light in genetic frontotemporal lobar degeneration
Zetterberg, H., Teunissen, C., van Swieten, J., Kuhle, J., Boxer, A., Rohrer, J. D., Mitic, L., Nicholson, A. M., Pearlman, R., McCaughey, S. M., et al. (2022) · Brain Communications · doi:10.1093/braincomms/fcac310 · Cited by 19 · see citing works
- Authors
- Oeckl, P., Weydt, P., Steinacker, P., Anderl-Straub, S., Nordin, F., Volk, A. E., Diehl-Schmid, J., Andersen, P. M., Kornhuber, J., Danek, A., Fassbender, K., Fliessbach, K., German Consortium for Frontotemporal Lobar Degeneration, Jahn, H., Lauer, M., Müller, K., Knehr, A., Prudlo, J., Schneider, A., Thal, D. R., Yilmazer-Hanke, D., Weishaupt, J. H., Ludolph, A. C., & Otto, M.
- Affiliations
- University Hospital Ulm (DE)
- Umeå University (SE)
- University Medical Center Hamburg-Eppendorf (DE)
- Friedrich-Alexander-Universität Erlangen-Nürnberg (DE)
- Ludwig-Maximilians-Universität München (DE)
- Saarland University (DE)
- University of Bonn (DE)
- Universität Hamburg (DE)
- University of Würzburg (DE)
- German Center for Neurodegenerative Diseases (DE)
- Universität Ulm (DE)
- Corresponding author
- Otto, Markus
- ORCID
- Venue
- Journal of Neurology, Neurosurgery & Psychiatry
- Publisher
- BMJ
- Published
- 2018-09-17
- Volume
- 90
- Issue
- 1
- Pages
- 4-10
- ISSN
- 0022-3050 (ISSN-L)
- 1468-330X
- OpenAlex
- W2890180591
- Cited by
- 139
- References
- 9
- Citations by year
- 2026: 6 · 2025: 22 · 2024: 7 · 2023: 18 · 2022: 27 · 2021: 18 · 2020: 19 · 2019: 17 · 2018: 5
- FWCI
- 10.02
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Journal of Neurology Neurosurgery & Psychiatry (publishedVersion)
- PubMed (publishedVersion)
- Lirias (KU Leuven) (submittedVersion, other-oa)
- Open access LMU (Ludwid Maxmilian's Universitat Munchen) (submittedVersion)
- mediaTUM – the media and publications repository of the Technical University Munich (Technical University Munich) (submittedVersion)
- HighWire Press Open Archive (submittedVersion)
- DZNE Pub (submittedVersion)
- Funders
- Swedish Brain Research Foundation
- Baden-Württemberg Stiftung (D.3830)
- Deutsche Forschungsgemeinschaft (SFB1279VO2028)
- Boehringer Ingelheim Ulm University BioCenter (D.5009)
- Vetenskapsrådet
- Fondation Thierry Latran
- European Commission (246513633190)
- Ulla-Carin Lindquist Foundation
- Bundesministerium für Bildung und Forschung (01GM1103AO1GI1007A)
- Knut och Alice Wallenbergs Stiftelse
- Fondation Charcot
- Bertil Hållsten Foundation
- JPND (01ED1202A01ED1203F01ED1512)
- Topics
- Health Sciences › Medicine › Neurology › Amyotrophic Lateral Sclerosis Research
- Life Sciences › Neuroscience › Neurology › Neuroinflammation and Neurodegeneration Mechanisms
- Health Sciences › Medicine › Physiology › Alzheimer's disease research and treatments
- Keywords
- amyotrophic lateral sclerosis, frontotemporal dementia, neuroinflammation, YKL-40, glial fibrillary acidic protein, cerebrospinal fluid biomarkers, blood biomarkers, asymptomatic mutation carriers, disease phases, clinical features
- MeSH terms
- Chitinase-3-Like Protein 1, Adult, Aged, Amyotrophic Lateral Sclerosis, Female, Glial Fibrillary Acidic Protein, Heterozygote, Hexosaminidases, Humans, Male, Middle Aged, Mutation, Case-Control Studies, Frontotemporal Dementia, Asymptomatic Diseases
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