Chitotriosidase as biomarker for early stage amyotrophic lateral sclerosis: a multicenter study

被引：17

作者：

Steinacker, Petra ^{[1
]}

Feneberg, Emily ^{[2
]}

Halbgebauer, Steffen ^{[1
]}

Witzel, Simon ^{[1
]}

Verde, Federico ^{[3
,4
,5
]}

Oeckl, Patrick ^{[1
]}

Van Damme, Philip ^{[6
,7
]}

Gaur, Nayana ^{[8
]}

Gray, Elizabeth ^{[2
]}

Grosskreutz, Julian ^{[8
]}

Jardel, Claude G. ^{[9
]}

Kachanov, Mykyta ^{[10
]}

Kuhle, Jens ^{[11
,12
,13
,14
]}

Lamari, Foudil ^{[9
]}

Maceski, Aleksandra ^{[11
,12
,13
,14
]}

Del Mar Amador, Maria ^{[15
]}

Mayer, Benjamin ^{[16
]}

Morelli, Claudia ^{[3
,4
]}

Petri, Susanne ^{[17
]}

Poesen, Koen ^{[18
,19
]}

Raaphorst, Joost ^{[20
]}

Salachas, Francois ^{[15
]}

Silani, Vincenzo ^{[3
,4
,5
]}

Turner, Martin R. ^{[2
]}

Verbeek, Marcel M. ^{[21
,22
]}

Volk, Alexander E. ^{[10
]}

Weishaupt, Jochen H. ^{[1
]}

Weydt, Patrick ^{[23
]}

Ludolph, Albert C. ^{[1
]}

Otto, Markus ^{[1
]}

机构：

[1] Ulm Univ, Dept Neurol, Ulm, Germany

[2] Univ Oxford, Nuffield Dept Clin Neurosci, Oxford, England

[3] IRCCS, Ist Auxol Italiano, Dept Neurol, Stroke Unit, Milan, Italy

[4] IRCCS, Ist Auxol Italiano, Lab Neurosci, Milan, Italy

[5] Univ Milan, Dino Ferrari Ctr, Dept Pathophysiol & Transplantat, Milan, Italy

[6] Univ Hosp Leuven, Dept Neurol, Leuven, Belgium

[7] Univ Leuven VIB, KU Leuven, Ctr Brain & Dis Res, Dept Neurosci,Expt Neurol Lab Neurobiol, Leuven, Belgium

[8] Jena Univ Hosp, Dept Neurol, Jena, Germany

[9] Hop Univ Pitie Salpeetriere Charles Foix, Dept Metab Biochem, Paris, France

[10] Univ Med Ctr Hamburg Eppendorf, Inst Human Genet, Hamburg, Germany

[11] Univ Basel, Dept Biomed, Neurol, Basel, Switzerland

[12] Univ Basel, Dept Med, Neurol, Basel, Switzerland

[13] Univ Basel, Dept Clin Res, Neurol, Basel, Switzerland

[14] Univ Hosp Basel, Basel, Switzerland

[15] Hop Univ Pitie Salpeetriere Charles Foix, Paris ALS Reference Ctr, Neurol Dis Dept, Paris, France

[16] Ulm Univ, Inst Epidemiol & Med Biometry, Ulm, Germany

[17] Hannover Med Sch, Dept Neurol, Hannover, Germany

[18] Katholieke Univ Leuven, Leuven Brain Inst, Lab Mol Neurobiomarker Res, Leuven, Belgium

[19] Univ Hosp Leuven, Lab Med, Leuven, Belgium

[20] Univ Amsterdam, Amsterdam UMC, Amsterdam Neurosci Inst, Dept Neurol, Amsterdam, Netherlands

[21] Radboud Univ Nijmegen, Med Ctr, Donders Inst Brain Cognit & Behav, Dept Neurol, Nijmegen, Netherlands

[22] Radboud Univ Nijmegen, Med Ctr, Donders Inst Brain Cognit & Behav, Dept Lab Med, Nijmegen, Netherlands

[23] Univ Bonn, Dept Neurodegenerat Disorders & Gerontopsychiat, Bonn, Germany

来源：

AMYOTROPHIC LATERAL SCLEROSIS AND FRONTOTEMPORAL DEGENERATION | 2021年 / 22卷 / 3-4期

基金：

英国医学研究理事会;

关键词：

Amyotrophic lateral sclerosis; prognostic biomarker; chitotriosidase; neurofilaments;

D O I：

10.1080/21678421.2020.1861023

中图分类号：

R74 [神经病学与精神病学];

学科分类号：

摘要：

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 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.

引用

页码：276 / 286

页数：11

共 36 条

[1] CSF biomarkers of neuroinflammation in distinct forms and subtypes of neurodegenerative dementia [J].