{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,6]],"date-time":"2026-11-06T17:56:10Z","timestamp":1793987770180,"version":"4.8.0"},"reference-count":39,"publisher":"BMJ","issue":"4","license":[{"start":{"date-parts":[[2020,1,14]],"date-time":"2020-01-14T00:00:00Z","timestamp":1578960000000},"content-version":"unspecified","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"funder":[{"DOI":"10.13039\/100005202","name":"Muscular Dystrophy Association","doi-asserted-by":"publisher","award":["MDA603370"],"award-info":[{"award-number":["MDA603370"]}],"id":[{"id":"10.13039\/100005202","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100009797","name":"Barrow Neurological Foundation","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100009797","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["bmj.com"],"crossmark-restriction":true},"short-container-title":["J Neurol Neurosurg Psychiatry"],"published-print":{"date-parts":[[2020,4]]},"abstract":"<jats:sec>\n                    <jats:title>Objective<\/jats:title>\n                    <jats:p>Amyotrophic lateral sclerosis (ALS) is a complex disease with numerous pathological mechanisms resulting in a heterogeneous patient population. Using biomarkers for particular disease mechanisms may enrich a homogeneous subset of patients. In this study, we quantified chitotriosidase (Chit-1) and chitinase-3-like protein 1 (CHI3L1), markers of glial activation, in cerebrospinal fluid (CSF) and plasma and determined the cell types that express CHI3L1 in ALS.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>Immunoassays were used to quantify Chit-1, CHI3L1 and phosphorylated neurofilament heavy chain levels in longitudinal CSF and matching plasma samples from 118 patients with ALS, 17 disease controls (DCs), and 24 healthy controls (HCs). Immunostaining was performed to identify and quantify CHI3L1-positive cells in tissue sections from ALS, DCs and non-neurological DCs.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>CSF Chit-1 exhibited increased levels in ALS as compared with DCs and HCs. CSF CHI3L1 levels were increased in ALS and DCs compared with HCs. No quantitative differences were noted in plasma for either chitinase. Patients with ALS with fast-progressing disease exhibited higher levels of CSF Chit-1 and CHI3L1 than patients with slow-progressing disease. Increased numbers of CHI3L1-positive cells were observed in postmortem ALS motor cortex as compared with controls, and these cells were identified as a subset of activated astrocytes located predominately in the white matter of the motor cortex and the spinal cord.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>CSF Chit-1 and CHI3L1 are significantly increased in ALS, and CSF Chit-1 and CHI3L1 levels correlate to the rate of disease progression. CHI3L1 is expressed by a subset of activated astrocytes predominately located in white matter.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1136\/jnnp-2019-321916","type":"journal-article","created":{"date-parts":[[2020,1,14]],"date-time":"2020-01-14T17:32:50Z","timestamp":1579023170000},"page":"350-358","update-policy":"https:\/\/doi.org\/10.1136\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":81,"title":["Cross-sectional and longitudinal measures of chitinase proteins in amyotrophic lateral sclerosis and expression of CHI3L1 in activated astrocytes"],"prefix":"10.1136","volume":"91","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-1869-1324","authenticated-orcid":false,"given":"Lucas","family":"Vu","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jiyan","family":"An","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tina","family":"Kovalik","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tania","family":"Gendron","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Leonard","family":"Petrucelli","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Robert","family":"Bowser","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"239","published-online":{"date-parts":[[2020,1,14]]},"reference":[{"key":"key-10.1136\/jnnp-2019-321916-1","doi-asserted-by":"crossref","first-page":"942","DOI":"10.1016\/S0140-6736(10)61156-7","article-title":"Amyotrophic lateral sclerosis","volume":"377","author":"Kiernan","year":"2011","journal-title":"The Lancet"},{"key":"key-10.1136\/jnnp-2019-321916-2","first-page":"146","article-title":"pNfH is a promising biomarker for ALS","volume":"14","author":"Ganesalingam","year":"2013","journal-title":"Amyotroph Lat Scl Fr"},{"key":"key-10.1136\/jnnp-2019-321916-3","doi-asserted-by":"crossref","first-page":"467","DOI":"10.1136\/jnnp-2012-303768","article-title":"Phosphorylated neurofilament heavy subunit (pNF-H) in peripheral blood and CSF as a potential prognostic biomarker in amyotrophic lateral sclerosis","volume":"84","author":"Boylan","year":"2013","journal-title":"J Neurol Neurosurg Psychiatry"},{"key":"key-10.1136\/jnnp-2019-321916-4","doi-asserted-by":"crossref","first-page":"538","DOI":"10.1080\/21678421.2019.1646769","article-title":"Neurofilaments in pre-symptomatic ALS and the impact of genotype","volume":"20","author":"Benatar","year":"2019","journal-title":"Amyotroph Lateral Scler Frontotemporal Degener"},{"key":"key-10.1136\/jnnp-2019-321916-5","doi-asserted-by":"crossref","first-page":"130","DOI":"10.1002\/ana.25276","article-title":"Neurofilament light: a candidate biomarker of presymptomatic amyotrophic lateral sclerosis and phenoconversion","volume":"84","author":"Benatar","year":"2018","journal-title":"Ann Neurol"},{"key":"key-10.1136\/jnnp-2019-321916-6","doi-asserted-by":"crossref","DOI":"10.1371\/journal.pone.0087398","article-title":"The extracellular domain of neurotrophin receptor p75 as a candidate biomarker for amyotrophic lateral sclerosis","volume":"9","author":"Shepheard","year":"2014","journal-title":"PLoS One"},{"key":"key-10.1136\/jnnp-2019-321916-7","doi-asserted-by":"crossref","first-page":"1137","DOI":"10.1212\/WNL.0000000000003741","article-title":"Urinary p75(ECD): A prognostic, disease progression, and pharmacodynamic biomarker in ALS","volume":"88","author":"Shepheard","year":"2017","journal-title":"Neurology"},{"key":"key-10.1136\/jnnp-2019-321916-8","doi-asserted-by":"crossref","DOI":"10.3389\/fnagi.2017.00068","article-title":"Als clinical trials review: 20 years of failure. are we any closer to Registering a new treatment?","volume":"9","author":"Petrov","year":"2017","journal-title":"Front Aging Neurosci"},{"key":"key-10.1136\/jnnp-2019-321916-9","doi-asserted-by":"crossref","DOI":"10.1212\/NXI.0000000000000100","article-title":"Randomized phase 2 trial of NP001-a novel immune regulator: safety and early efficacy in ALS","volume":"2","author":"Miller","year":"2015","journal-title":"Neurol Neuroimmunol Neuroinflamm"},{"key":"key-10.1136\/jnnp-2019-321916-10","doi-asserted-by":"crossref","first-page":"601","DOI":"10.3109\/21678421.2014.951940","article-title":"NP001 regulation of macrophage activation markers in ALS: a phase I clinical and biomarker study","volume":"15","author":"Miller","year":"2014","journal-title":"Amyotroph Lateral Scler Frontotemporal Degener"},{"key":"key-10.1136\/jnnp-2019-321916-11","doi-asserted-by":"crossref","first-page":"117727190700200","DOI":"10.1177\/117727190700200023","article-title":"Human chitinases and chitinase-like proteins as indicators for inflammation and cancer","volume":"2","author":"Kzhyshkowska","year":"2007","journal-title":"Biomark Insights"},{"key":"key-10.1136\/jnnp-2019-321916-12","doi-asserted-by":"crossref","first-page":"141","DOI":"10.1042\/BST20170108","article-title":"Chitinase-Like proteins as regulators of innate immunity and tissue repair: helpful lessons for asthma?","volume":"46","author":"Sutherland","year":"2018","journal-title":"Biochem Soc Trans"},{"key":"key-10.1136\/jnnp-2019-321916-13","doi-asserted-by":"crossref","first-page":"399","DOI":"10.1016\/j.imbio.2015.11.014","article-title":"Chitinases and immunity: ancestral molecules with new functions","volume":"221","author":"Di Rosa","year":"2016","journal-title":"Immunobiology"},{"key":"key-10.1136\/jnnp-2019-321916-14","doi-asserted-by":"crossref","first-page":"1251","DOI":"10.1177\/1352458514561906","article-title":"Chitinase 3-like proteins as diagnostic and prognostic biomarkers of multiple sclerosis","volume":"21","author":"Hinsinger","year":"2015","journal-title":"Mult Scler"},{"key":"key-10.1136\/jnnp-2019-321916-15","doi-asserted-by":"crossref","DOI":"10.1186\/1742-2094-7-34","article-title":"In vivo CHI3L1 (YKL-40) expression in astrocytes in acute and chronic neurological diseases","volume":"7","author":"Bonneh-Barkay","year":"2010","journal-title":"J Neuroinflammation"},{"key":"key-10.1136\/jnnp-2019-321916-16","doi-asserted-by":"crossref","first-page":"297","DOI":"10.1159\/000362164","article-title":"Increased levels of chitotriosidase and YKL-40 in cerebrospinal fluid from patients with Alzheimer's disease","volume":"4","author":"Ros\u00e9n","year":"2014","journal-title":"Dement Geriatr Cogn Dis Extra"},{"key":"key-10.1136\/jnnp-2019-321916-17","doi-asserted-by":"crossref","first-page":"245","DOI":"10.1016\/j.jns.2014.12.016","article-title":"Chitotriosidase and lysosomal enzymes as potential biomarkers of disease progression in amyotrophic lateral sclerosis: a survey clinic-based study","volume":"348","author":"Pagliardini","year":"2015","journal-title":"J Neurol Sci"},{"key":"key-10.1136\/jnnp-2019-321916-18","doi-asserted-by":"crossref","DOI":"10.1186\/1559-0275-10-19","article-title":"Chitotriosidase - a putative biomarker for sporadic amyotrophic lateral sclerosis","volume":"10","author":"Varghese","year":"2013","journal-title":"Clin Proteomics"},{"key":"key-10.1136\/jnnp-2019-321916-19","doi-asserted-by":"crossref","first-page":"239","DOI":"10.1136\/jnnp-2017-317138","article-title":"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","volume":"89","author":"Steinacker","year":"2018","journal-title":"J Neurol Neurosurg Psychiatry"},{"key":"key-10.1136\/jnnp-2019-321916-20","doi-asserted-by":"crossref","first-page":"258","DOI":"10.1002\/ana.25143","article-title":"Cerebrospinal fluid macrophage biomarkers in amyotrophic lateral sclerosis","volume":"83","author":"Thompson","year":"2018","journal-title":"Ann Neurol"},{"key":"key-10.1136\/jnnp-2019-321916-21","doi-asserted-by":"crossref","first-page":"1215","DOI":"10.1136\/jnnp-2019-320442","article-title":"Csf chitinase proteins in amyotrophic lateral sclerosis","volume":"90","author":"Thompson","year":"2019","journal-title":"J Neurol Neurosurg Psychiatry"},{"key":"key-10.1136\/jnnp-2019-321916-22","first-page":"1338","article-title":"Inflammatory markers in cerebrospinal fluid: independent prognostic biomarkers in amyotrophic lateral sclerosis?","volume":"90","author":"Gille","year":"2019","journal-title":"J Neurol Neurosurg Psychiatry"},{"key":"key-10.1136\/jnnp-2019-321916-23","doi-asserted-by":"crossref","first-page":"162","DOI":"10.1016\/j.mcn.2017.10.001","article-title":"Chi3L1 and CHI3L2 overexpression in motor cortex and spinal cord of sALS patients","volume":"85","author":"Sanfilippo","year":"2017","journal-title":"Mol Cell Neurosci"},{"key":"key-10.1136\/jnnp-2019-321916-24","doi-asserted-by":"crossref","first-page":"4486","DOI":"10.1021\/acs.jproteome.5b00804","article-title":"Label-Free LC\u2013MS\/MS proteomic analysis of cerebrospinal fluid identifies Protein\/Pathway alterations and candidate biomarkers for amyotrophic lateral sclerosis","volume":"14","author":"Collins","year":"2015","journal-title":"J Proteome Res"},{"key":"key-10.1136\/jnnp-2019-321916-25","doi-asserted-by":"crossref","first-page":"1461","DOI":"10.1111\/j.1471-4159.2005.03478.x","article-title":"Proteomic profiling of cerebrospinal fluid identifies biomarkers for amyotrophic lateral sclerosis","volume":"95","author":"Ranganathan","year":"2005","journal-title":"J Neurochem"},{"key":"key-10.1136\/jnnp-2019-321916-26","doi-asserted-by":"crossref","first-page":"139","DOI":"10.1002\/ana.24980","article-title":"Phosphorylated neurofilament heavy chain: A biomarker of survival for C9ORF 72 -associated amyotrophic lateral sclerosis","volume":"82","author":"Gendron","year":"2017","journal-title":"Ann Neurol"},{"key":"key-10.1136\/jnnp-2019-321916-27","doi-asserted-by":"crossref","first-page":"227","DOI":"10.1007\/s00401-017-1785-8","article-title":"Artificial intelligence in neurodegenerative disease research: use of IBM Watson to identify additional RNA-binding proteins altered in amyotrophic lateral sclerosis","volume":"135","author":"Bakkar","year":"2018","journal-title":"Acta Neuropathol"},{"key":"key-10.1136\/jnnp-2019-321916-28","doi-asserted-by":"crossref","first-page":"839","DOI":"10.1148\/radiology.148.3.6878708","article-title":"A method of comparing the areas under receiver operating characteristic curves derived from the same cases","volume":"148","author":"Hanley","year":"1983","journal-title":"Radiology"},{"key":"key-10.1136\/jnnp-2019-321916-29","doi-asserted-by":"crossref","first-page":"565","DOI":"10.1136\/jnnp-2014-307672","article-title":"Plasma neurofilament heavy chain levels and disease progression in amyotrophic lateral sclerosis: insights from a longitudinal study","volume":"86","author":"Lu","year":"2015","journal-title":"J Neurol Neurosurg Psychiatry"},{"key":"key-10.1136\/jnnp-2019-321916-30","first-page":"12","article-title":"Neurofilaments in the diagnosis of motoneuron diseases: a prospective study on 455 patients","volume":"87","author":"Steinacker","year":"2016","journal-title":"J Neurol Neurosurg Psychiatry"},{"key":"key-10.1136\/jnnp-2019-321916-31","doi-asserted-by":"crossref","first-page":"152","DOI":"10.1002\/ana.24552","article-title":"Neurofilament levels as biomarkers in asymptomatic and symptomatic familial amyotrophic lateral sclerosis","volume":"79","author":"Weydt","year":"2016","journal-title":"Ann Neurol"},{"key":"key-10.1136\/jnnp-2019-321916-32","doi-asserted-by":"crossref","DOI":"10.1186\/s12883-016-0689-x","article-title":"Assessment of a multiple biomarker panel for diagnosis of amyotrophic lateral sclerosis","volume":"16","author":"Chen","year":"2016","journal-title":"BMC Neurol"},{"key":"key-10.1136\/jnnp-2019-321916-33","doi-asserted-by":"crossref","first-page":"4","DOI":"10.1136\/jnnp-2018-318868","article-title":"Different neuroinflammatory profile in amyotrophic lateral sclerosis and frontotemporal dementia is linked to the clinical phase","volume":"90","author":"Oeckl","year":"2019","journal-title":"J Neurol Neurosurg Psychiatry"},{"key":"key-10.1136\/jnnp-2019-321916-34","doi-asserted-by":"crossref","first-page":"251","DOI":"10.1038\/nn2047","article-title":"Astrocytes as determinants of disease progression in inherited amyotrophic lateral sclerosis","volume":"11","author":"Yamanaka","year":"2008","journal-title":"Nat Neurosci"},{"key":"key-10.1136\/jnnp-2019-321916-35","doi-asserted-by":"crossref","first-page":"2367","DOI":"10.18632\/aging.101551","article-title":"Ykl40 in sporadic amyotrophic lateral sclerosis: cerebrospinal fluid levels as a prognosis marker of disease progression","volume":"10","author":"Andr\u00e9s-Benito","year":"2018","journal-title":"Aging"},{"key":"key-10.1136\/jnnp-2019-321916-36","doi-asserted-by":"crossref","first-page":"409","DOI":"10.1016\/j.nicl.2015.01.009","article-title":"Increased in vivo glial activation in patients with amyotrophic lateral sclerosis: Assessed with [11C]-PBR28","volume":"7","author":"Z\u00fcrcher","year":"2015","journal-title":"Neuroimage"},{"key":"key-10.1136\/jnnp-2019-321916-37","doi-asserted-by":"crossref","first-page":"263","DOI":"10.1097\/00005072-199105000-00008","article-title":"Reactive astrogliosis is widespread in the subcortical white matter of amyotrophic lateral sclerosis brain","volume":"50","author":"Kushner","year":"1991","journal-title":"J Neuropathol Exp Neurol"},{"key":"key-10.1136\/jnnp-2019-321916-38","doi-asserted-by":"crossref","first-page":"161","DOI":"10.1016\/j.neuroscience.2013.10.050","article-title":"White matter astrocytes in health and disease","volume":"276","author":"Lundgaard","year":"2014","journal-title":"Neuroscience"},{"key":"key-10.1136\/jnnp-2019-321916-39","doi-asserted-by":"crossref","DOI":"10.1186\/s12974-017-0893-7","article-title":"YKL-40 (Chitinase 3-like I) is expressed in a subset of astrocytes in Alzheimer\u2019s disease and other tauopathies","volume":"14","author":"Querol-Vilaseca","year":"2017","journal-title":"J Neuroinflammation"}],"container-title":["Journal of Neurology, Neurosurgery &amp; Psychiatry"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/syndication.highwire.org\/content\/doi\/10.1136\/jnnp-2019-321916","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2020,9,26]],"date-time":"2020-09-26T00:50:50Z","timestamp":1601081450000},"score":1,"resource":{"primary":{"URL":"https:\/\/jnnp.bmj.com\/lookup\/doi\/10.1136\/jnnp-2019-321916"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2020,1,14]]},"references-count":39,"journal-issue":{"issue":"4","published-online":{"date-parts":[[2020,3,16]]},"published-print":{"date-parts":[[2020,4]]}},"alternative-id":["10.1136\/jnnp-2019-321916"],"URL":"https:\/\/doi.org\/10.1136\/jnnp-2019-321916","relation":{},"ISSN":["0022-3050","1468-330X"],"issn-type":[{"value":"0022-3050","type":"print"},{"value":"1468-330X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2020,1,14]]}}}