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  Chitotriosidase (CHIT1) is increased in microglia and macrophages in spinal cord of amyotrophic lateral sclerosis and cerebrospinal fluid levels correlate with disease severity and progression

Steinacker, P., Verde, F., Fang, L., Feneberg, E., Oeckl, P., Roeber, S., et al. (2018). Chitotriosidase (CHIT1) is increased in microglia and macrophages in spinal cord of amyotrophic lateral sclerosis and cerebrospinal fluid levels correlate with disease severity and progression. Journal of Neurology, Neurosurgery & Psychiatry, 89(3), 228-229. doi:10.1136/jnnp-2017-317138.

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Item Permalink: https://hdl.handle.net/21.11116/0000-0001-25AF-1 Version Permalink: https://hdl.handle.net/21.11116/0000-0003-A55A-E
Genre: Journal Article

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 Creators:
Steinacker, Petra1, Author
Verde, Federico1, Author
Fang, Lubin1, Author
Feneberg, Emily1, Author
Oeckl, Patrick1, Author
Roeber, Sigrun1, Author
Anderl-Straub, Sarah1, Author
Danek, Adrian1, Author
Diehl-Schmid, Janine1, Author
Fassbender, Klaus1, Author
Fliessbach, Klaus1, Author
Foerstl, Hans1, Author
Giese, Armin1, Author
Jahn, Holger1, Author
Kassubek, Jan1, Author
Kornhuber, Johannes1, Author
Landwehrmeyer, G. Bernhard1, Author
Lauer, Martin1, Author
Pinkhardt, Elmar Hans1, Author
Prudlo, Johannes1, Author
Rosenbohm, Angela1, AuthorSchneider, Anja1, AuthorSchroeter, Matthias L.2, Author           Tumani, Hayrettin1, Authorvon Arnim, Christine A. F.1, AuthorWeishaupt, Jochen1, AuthorWeydt, Patrick1, AuthorLudolph, Albert C.1, AuthorHanke, Deniz Yilmazer1, AuthorOtto, Markus1, AuthorFTLDc Study Group, Author               more..
Affiliations:
1External Organizations, ou_persistent22              
2Department Neurology, MPI for Human Cognitive and Brain Sciences, Max Planck Society, ou_634549              

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 Abstract: Objectives Neurochemical 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).

Methods Altogether 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.

Results In 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).

Conclusions CHIT1 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.

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Language(s): eng - English
 Dates: 2017-09-252017-08-232017-10-042017-11-152018-03
 Publication Status: Issued
 Pages: -
 Publishing info: -
 Table of Contents: -
 Rev. Type: Peer
 Identifiers: DOI: 10.1136/jnnp-2017-317138
PMID: 29142138
Other: Epub 2017
 Degree: -

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Project name : -
Grant ID : -
Funding program : SOPHIA
Funding organization : Joint Programme – Neurodegenerative Disease Research (JPND)
Project name : -
Grant ID : -
Funding program : BiomarkAPD
Funding organization : Joint Programme – Neurodegenerative Disease Research (JPND)
Project name : -
Grant ID : -
Funding program : PreFrontAls
Funding organization : Joint Programme – Neurodegenerative Disease Research (JPND)
Project name : Nanosystems for the early Diagnosis of Neurodegenerative diseases / NADINE
Grant ID : 246513
Funding program : Funding Programme 7
Funding organization : European Commission (EC)
Project name : Conservative iron chelation as a disease-modifying strategy in Parkinson’s disease: a multicentric, parallel-group, placebo-controlled, randomized clinical trial of deferiprone / FAIR-PARK II
Grant ID : 633190
Funding program : Horizon 2020
Funding organization : European Commission (EC)
Project name : -
Grant ID : D.3830
Funding program : -
Funding organization : Foundation of the State Baden-Württemberg
Project name : -
Grant ID : -
Funding program : -
Funding organization : Thierry Latran Foundation
Project name : -
Grant ID : D.5009
Funding program : -
Funding organization : Boehringer Ingelheim Ulm University BioCenter
Project name : German Consortium for Frontotemporal Lobar Degeneration
Grant ID : O1GI1007A
Funding program : -
Funding organization : German Federal Ministry of Education and Research (BMBF)
Project name : -
Grant ID : 01GM1103A
Funding program : -
Funding organization : German Federal Ministry for Education and Research (BMBF)

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Title: Journal of Neurology, Neurosurgery & Psychiatry
Source Genre: Journal
 Creator(s):
Affiliations:
Publ. Info: London : British Medical Association
Pages: - Volume / Issue: 89 (3) Sequence Number: - Start / End Page: 228 - 229 Identifier: ISSN: 0022-3050
CoNE: https://pure.mpg.de/cone/journals/resource/111085522793000