• Petra Steinacker, Federico Verde, Lubin Fang, Emily Feneberg, Patrick Oeckl, Sigrun Roeber, Sarah Anderl-Straub, Adrian Danek, Janine Diehl-Schmid, Klaus Fassbender, Klaus Fliessbach, Hans Foerstl, Armin Giese, Holger Jahn, Jan Kassubek, Johannes Kornhuber, G Bernhard Landwehrmeyer, Martin Lauer, Elmar Hans Pinkhardt, Johannes Prudlo, Angela Rosenbohm, Anja Schneider, Matthias L Schroeter, Hayrettin Tumani, von Arnim Christine A F CAF Department of Neurology, University of Ulm, Ulm, Germany., Jochen Weishaupt, Patrick Weydt, Albert C Ludolph, Deniz Yilmazer Hanke, Markus Otto, and FTLDc study group.
• Department of Neurology, University of Ulm, Ulm, Germany.
• J. Neurol. Neurosurg. Psychiatr. 2018 Mar 1; 89 (3): 239-247.

ObjectivesNeurochemical markers of amyotrophic lateral sclerosis (ALS) that reflect underlying disease mechanisms might help in diagnosis, staging and prediction of outcome. We aimed at determining the origin and differential diagnostic and prognostic potential of the putative marker of microglial activation chitotriosidase (CHIT1).MethodsAltogether 316 patients were included, comprising patients with sporadic ALS, ALS mimics (disease controls (DCo)), frontotemporal lobar degeneration (FTLD), Creutzfeldt-Jakob disease (CJD), Alzheimer's disease (AD), Parkinson's disease (PD) and healthy controls (Con). CHIT1 and neurofilament levels were determined in cerebrospinal fluid (CSF) and blood and analysed with regard to diagnostic sensitivity and specificity and prognostic performance. Additionally, postmortem tissue was analysed for CHIT1 expression.ResultsIn ALS, CHIT1 CSF levels were higher compared with Con (p<0.0001), DCo (p<0.05) and neurodegenerative diseases (AD p<0.05, PD p<0.01, FTLD p<0.0001) except CJD. CHIT1 concentrations were correlated with ALS disease progression and severity but not with the survival time, as did neurofilaments. Serum CHIT1 levels were not different in ALS compared with any other study group. In the spinal cord of patients with ALS, but not Con, AD or CJD cases, CHIT1 was expressed in the corticospinal tract and CHIT1 staining colocalised with markers of microglia (IBA1) and macrophages (CD68).ConclusionsCHIT1 concentrations in the CSF of patients with ALS may reflect the extent of microglia/macrophage activation in the white matter of the spinal cord. CHIT1 could be a potentially useful marker for differential diagnosis and prediction of disease progression in ALS and, therefore, seems suitable as a supplemental marker for patient stratification in therapeutic trials.© Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2018. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

39 keywords...

hide…