{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,14]],"date-time":"2026-10-14T06:37:43Z","timestamp":1791959863830,"version":"4.3.4"},"reference-count":24,"publisher":"BMJ","issue":"11","funder":[{"DOI":"10.13039\/501100000265","name":"Medical Research Council","doi-asserted-by":"publisher","award":["Medical Research Council & Motor Neurone Disease A"],"award-info":[{"award-number":["Medical Research Council & Motor Neurone Disease A"]}],"id":[{"id":"10.13039\/501100000265","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["bmj.com"],"crossmark-restriction":true},"short-container-title":["J Neurol Neurosurg Psychiatry"],"accepted":{"date-parts":[[2019,4,23]]},"published-print":{"date-parts":[[2019,11]]},"abstract":"<jats:sec>\n<jats:title>Objective<\/jats:title>\n<jats:p>To evaluate the classifier performance, clinical and biochemical correlations of cerebrospinal fluid (CSF) levels of the chitinase proteins Chitotriosidase-1 (CHIT1), Chitinase-3-like protein 1 (CHI3L1) and Chitinase-3-like protein 2 (CHI3L2) in amyotrophic lateral sclerosis (ALS).<\/jats:p>\n<\/jats:sec>\n<jats:sec>\n<jats:title>Methods<\/jats:title>\n<jats:p>CSF levels of CHIT1, CHI3L1, CHI3L2, phosphorylated neurofilament heavy chain (pNFH) and C-reactive protein were measured by ELISA in a longitudinal cohort of patients with ALS (n=82), primary lateral sclerosis (PLS, n=10), ALS-mimic conditions (n=12), healthy controls (n=25) and asymptomatic carriers of ALS-causing genetic mutations (AGC; n=5).<\/jats:p>\n<\/jats:sec>\n<jats:sec>\n<jats:title>Results<\/jats:title>\n<jats:p>\nCSF CHIT1, CHI3L1 and CHI3L2 were elevated in patients with ALS compared with healthy controls (p&lt;0.001) and ALS-mimics (CHIT1, p&lt;0.001; CHI3L1, p=0.017; CHI3L2, p&lt;0.001). CHIT1 and CHI3L2 were elevated in ALS compared with PLS (CHIT1, p=0.021; CHI3L1, p=0.417; CHI3L2, p&lt;0.001). Chitinase levels were similar in AGCs and healthy controls. Chitinase proteins distinguished ALS from healthy controls (area under the curve (AUC): CHIT1 0.92; CHI3L1 0.80; CHI3L2 0.90), mimics (AUC: CHIT1 0.84; CHI3L1 0.73; CHI3L2 0.88) and, to a lesser extent, PLS (AUC: CHIT 0.73; CHI3L1 0.51; CHI3L2 0.82) but did not outperform pNFH. CHIT1 and CHI3L2 correlated with disease progression rate (Pearson\u2019s\n<jats:italic>r<\/jats:italic>\n=0.49, p&lt;0.001;\n<jats:italic>r<\/jats:italic>\n=0.42, p&lt;0.001, respectively). CHI3L1 correlated with degree of cognitive dysfunction (\n<jats:italic>r<\/jats:italic>\n=\u22120.25, p=0.038). All chitinases correlated with pNFH. CHIT1 levels were associated with survival in multivariate models. Chitinase levels were longitudinally stable.\n<\/jats:p>\n<\/jats:sec>\n<jats:sec>\n<jats:title>Conclusions<\/jats:title>\n<jats:p>CSF chitinase proteins may have limited value as independent diagnostic and stratification biomarkers in ALS, but offer a window into non-autonomous mechanisms of motor neuronal loss in ALS, specifically in assessing response to therapies targeting neuroinflammatory pathways.<\/jats:p>\n<\/jats:sec>","DOI":"10.1136\/jnnp-2019-320442","type":"journal-article","created":{"date-parts":[[2019,5,23]],"date-time":"2019-05-23T21:24:25Z","timestamp":1558646665000},"page":"1215-1220","update-policy":"https:\/\/doi.org\/10.1136\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":102,"title":["CSF chitinase proteins in amyotrophic lateral sclerosis"],"prefix":"10.1136","volume":"90","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-1063-3277","authenticated-orcid":false,"given":"Alexander G","family":"Thompson","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elizabeth","family":"Gray","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alexander","family":"Bampton","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dominika","family":"Raciborska","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kevin","family":"Talbot","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0267-3180","authenticated-orcid":false,"given":"Martin R","family":"Turner","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"239","published-online":{"date-parts":[[2019,5,23]]},"reference":[{"key":"2024120315300679000_90.11.1215.1","doi-asserted-by":"crossref","first-page":"162","DOI":"10.1056\/NEJMra1603471","article-title":"Amyotrophic lateral sclerosis","volume":"377","author":"Brown","year":"2017","journal-title":"N Engl J Med Overseas Ed"},{"key":"2024120315300679000_90.11.1215.2","doi-asserted-by":"crossref","unstructured":"Talbot K , Feneberg E , Scaber J , et al . 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