• Patrick Oeckl, Patrick Weydt, Petra Steinacker, Sarah Anderl-Straub, Frida Nordin, Alexander E Volk, Janine Diehl-Schmid, Peter M Andersen, Johannes Kornhuber, Adrian Danek, Klaus Fassbender, Klaus Fliessbach, German Consortium for Frontotemporal Lobar Degeneration, Holger Jahn, Martin Lauer, Kathrin Müller, Antje Knehr, Johannes Prudlo, Anja Schneider, Dietmar R Thal, Deniz Yilmazer-Hanke, Jochen H Weishaupt, Albert C Ludolph, and Markus Otto.
• Department of Neurology, Ulm University Hospital, Ulm, Germany.
• J. Neurol. Neurosurg. Psychiatr. 2019 Jan 1; 90 (1): 4-10.

ObjectiveTo investigate the role of neuroinflammation in asymptomatic and symptomatic amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD) mutation carriers.MethodsThe 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.ResultsCSF 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).ConclusionOur 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.© Author(s) (or their employer(s)) 2019. No commercial re-use. See rights and permissions. Published by BMJ.

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