Different neuroinflammatory profile in amyotrophic lateral sclerosis and frontotemporal dementia is linked to the clinical phase

• Published in: Journal of neurology, neurosurgery and psychiatry Vol. 90; no. 1; pp. 4 - 10
• Main Authors: Oeckl, Patrick, Weydt, Patrick, Steinacker, Petra, Anderl-Straub, Sarah, Nordin, Frida, Volk, Alexander E, Diehl-Schmid, Janine, Andersen, Peter M, Kornhuber, Johannes, Danek, Adrian, Fassbender, Klaus, Fliessbach, Klaus, Jahn, Holger, Lauer, Martin, Müller, Kathrin, Knehr, Antje, Prudlo, Johannes, Schneider, Anja, Thal, Dietmar R, Yilmazer-Hanke, Deniz, Weishaupt, Jochen H, Ludolph, Albert C, Otto, Markus
• Format: Journal Article
• Language: English
• Published: England BMJ Publishing Group LTD 01.01.2019
• Subjects: Adult; Age; Aged; Alzheimer's disease; Amyotrophic lateral sclerosis; Amyotrophic Lateral Sclerosis - blood; Amyotrophic Lateral Sclerosis - cerebrospinal fluid; Amyotrophic Lateral Sclerosis - immunology; Asymptomatic Diseases; Biomarkers; Case-Control Studies; Cerebrospinal fluid; Chitinase; Chitinase-3-Like Protein 1 - blood; Chitinase-3-Like Protein 1 - cerebrospinal fluid; Chitinase-3-Like Protein 1 - immunology; Dementia; Female; Frontotemporal Dementia - blood; Frontotemporal Dementia - cerebrospinal fluid; Frontotemporal Dementia - immunology; Genes; Glial Fibrillary Acidic Protein - blood; Glial Fibrillary Acidic Protein - cerebrospinal fluid; Glial Fibrillary Acidic Protein - immunology; Heterozygote; Hexosaminidases - blood; Hexosaminidases - cerebrospinal fluid; Hexosaminidases - immunology; Humans; Male; Middle Aged; Mutation; Neurology; Patients; Proteins; Proteomics; CHIT1; frontotemporal dementia; neuroinflammation; amyotrophic lateral sclerosis; cerebrospinal fluid; GFAP
• ISSN: 0022-3050; 1468-330X; 1468-330X
• DOI: 10.1136/jnnp-2018-318868

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.