Abstract
Objective: Levels of chitotriosidase (CHIT1) are increased in the cerebrospinal fluid (CSF) of amyotrophic lateral sclerosis (ALS) patients reflecting microglial activation. Here, we determine the diagnostic and prognostic potential of CHIT1 for early symptomatic ALS. Methods: Overall, 275 patients from 8 European neurological centers were examined. We included ALS with <6 and >6 months from symptom onset, other motoneuron diseases (oMND), ALS mimics (DCon) and non-neurodegenerative controls (Con). CSF CHIT1 levels were analyzed for diagnostic power and association with progression and survival in comparison to the benchmark neurofilament. The 24-bp duplication polymorphism of CHIT1 was analyzed in a subset of patients (N = 65). Results: Homozygous CHIT1 duplication mutation carriers (9%) invariably had undetectable CSF CHIT1 levels, while heterozygous carriers had similar levels as patients with wildtype CHIT1 (p = 0.414). In both early and late symptomatic ALS CHIT1 levels was increased, did not correlate with patients’ progression rates, and was higher in patients diagnosed with higher diagnostic certainty. Neurofilament levels correlated with CHIT1 levels and prevailed over CHIT1 regarding diagnostic performance. Both CHIT1 and neurofilaments were identified as independent predictors of survival in late but not early symptomatic ALS. Evidence is provided that CHIT1 predicts progression in El Escorial diagnostic category in the group of ALS cases with a short duration. Conclusions: CSF CHIT1 level may have additional value in the prognostication of ALS patients with a short history of symptoms classified in diagnostic categories of lower clinical certainty. To fully interpret apparently low CHIT1 levels knowledge of CHIT1 genotype is needed.
| Originalsprache | Englisch |
|---|---|
| Zeitschrift | Amyotrophic Lateral Sclerosis and Frontotemporal Degeneration |
| Jahrgang | 22 |
| Ausgabenummer | 3-4 |
| Seiten (von - bis) | 276-286 |
| Seitenumfang | 11 |
| ISSN | 2167-8421 |
| DOIs | |
| Publikationsstatus | Veröffentlicht - 2021 |
Fördermittel
This study was supported by the EU Joint Programme–Neurodegenerative Diseases (JPND) research networks under Grants Prefrontals [01ED1512], GENF-Prox [01ED2008A], and ONWebDUALS; the German Federal Ministry of Education and Research under Grant [FTLDc O1GI1007A]; the foundation of the state Baden-Württemberg under [Grant D.3830]; the Thierry Latran foundation; the ALS Association; Boehringer Ingelheim Ulm University BioCenter under [Grant D.5009]; a TBM grant from FWO-Vlaanderen [n° T003519N]; by the German Society for Muscle Diseases (DGM); the German Neuromuscular Society; the German Israeli Foundation (GIF) for Scientific Research and Development. PVD holds a senior clinical investigatorship of FWO-Vlaanderen and is supported by E. von Behring Chair for Neuromuscular and Neurodegenerative Disorders, the ALS Liga België and the KU Leuven funds "Een Hart voor ALS", "Laeversfonds voor ALS Onderzoek" and the "Valéry Perrier Race against ALS Fund". Several authors of this publication are member of the European Reference Network for Rare Neuromuscular Diseases (ERN-NMD). VS receives or has received research supports from the Italian Ministry of Health, AriSLA (Fondazione Italiana di Ricerca per la SLA), and E-Rare Joint Transnational Call. MRT is funded by the Motor Neurone Disease Association. For their excellent technical assistance, we are grateful to Stephen Meier, Sandra Hübsch, Dagmar Schattauer, Alice Beer, and Mehtap Türedi. We are deeply indebted to the patients for participating in this study.
Strategische Forschungsbereiche und Zentren
- Forschungsschwerpunkt: Gehirn, Hormone, Verhalten - Center for Brain, Behavior and Metabolism (CBBM)
- Zentren: Neuromuskuläres Zentrum Schleswig-Holstein
UN SDGs
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