Chitotriosidase and lysosomal enzymes as potential biomarkers of disease progression in amyotrophic lateral sclerosis: A survey clinic-based study

Pagliardini, Veronica; Pagliardini, Severo; Corrado, Lucia; Lucenti, Ausiliatrice; Panigati, Laura; Bersano, Enrica; Servo, Serena; Cantello, Roberto; D’Alfonso, Sandra; Mazzini, Letizia

doi:10.1016/j.jns.2014.12.016

Cited by 37 publications

(44 citation statements)

References 33 publications

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“…However, as there are marked differences in CHIT1 levels in the neurodegenerative diseases investigated, CHIT1 might be a more specific biomarker for a reliable detection of immune activation, and therefore might be used in upcoming therapeutic trials addressing this mechanism. Despite the previously reported marked increase of CHIT1 activity in the blood of patients with ALS,16 we could not detect differences in concentrations of this enzyme in the serum of ALS, DCo and Con cases. Although data in paired CSF-serum samples are currently unavailable, different and potentially independent mechanisms may drive changes in CHIT1 protein levels and activity in CSF and blood.…”

Section: Discussioncontrasting

confidence: 99%

“…In studies with small patient cohorts, it was recently reported that chitotriosidase (CHIT1) is increased in the cerebrospinal fluid (CSF) of patients with ALS compared with healthy and neurological controls14 15 and that blood CHIT1 activity correlates with disease progression 16. CHIT1 is expressed by cells of the monocyte/macrophage lineage and cleaves N-acetyl glucosamine polymers (mainly found in chitin).…”

Section: Introductionmentioning

confidence: 99%

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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

Verde

Fang

et al. 2017

J Neurol Neurosurg Psychiatry

107

105

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Section: Discussioncontrasting

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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

Verde

Fang

et al. 2017

J Neurol Neurosurg Psychiatry

107

105

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show abstract

“…Further studies to investigate the presence of ChT substrate in CNS of ALS's patients are necessary. We have not demonstrated any association between ChT activity in CSF with the course, severity or progression of the disease as it has been reported by other authors [18,29], which could be explained for the limited sample size.…”

Section: Discussioncontrasting

confidence: 72%

“…This evidence suggests the overproduction of this enzyme exerts a deleterious effect in many degenerative disorders [15,[37][38][39][40]. Regarding ALS, some studies have previously shown an increased blood ChT activity suggesting this enzyme as a potential biomarker [29], and elevated ChT levels in ALS-CSF proposing a role for the enzyme in the disease pathogenesis [16,18]. Chitin, the natural substrate of ChT in unvertebrates animals, is an insoluble N-acetylglucosamine polymer and it is uncertain whether ChT activity in CSF reflects only a microglia activation or if some chitin-like polysaccharides at CNS could be the substrate of this enzyme [17].…”

Section: Discussionmentioning

confidence: 89%

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Evaluation of Chitotriosidase and CC-Chemokine Ligand 18 as Biomarkers of Microglia Activation in Amyotrophic Lateral Sclerosis

et al. 2018

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Background: The development of biomarkers for use in diagnosing, monitoring disease progression and analyzing therapeutic trials response in amyotrophic lateral sclerosis (ALS) is essential. Objective: The aim of this study was to identify inflammatory factors in plasma or cerebrospinal fluid (CSF) from patients with ALS with particular attention to specific markers of microglia activation as chitotriosidase (ChT) and chemokine (C-C motif) ligand 18 (CCL18) to determine its potential as ALS biomarkers. Methods: We studied CSF and plasma samples from 32 patients and 42 healthy controls. We assayed the ChT activity by a spectrofluorometric method and protein levels of other inflammatory biomarkers (tumor necrosis factor [TNF]-alpha, interleukin [IL]-6 and CCL18) by enzyme-linked immunosorbent assay. CHIT1 gene polymorphism in exon 10 (c.1049_1072dup24) encoding inactive ChT enzyme was genotyped in all subjects. Results: ChT activity and TNF-alpha protein levels were significantly higher in CSF of ALS patients, but we found no correlation with the severity and progression of the disease. Nevertheless, we did not found any differences in CCL18 or IL-6 protein levels between both groups in CSF or plasma. In our sample, only 3% of subjects were homozygous carriers for the CHIT1 exon 10 duplication associated with defective enzyme. Conclusions: High ChT activity in CSF of patients with ALS may reflect microglia activation and could be a potential biomarker of the disease. We did not find any significant difference regarding CCL-18, another specific marker of microglia activation that is related with M2-like microglia phenotype. Deepening the understanding of the activation state of microglia (M1 and M2) may contribute to the knowledge about the specific role of neuroinflammation in ALS and future therapeutic strategies.

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Chitotriosidase is a biomarker for adult‐onset leukoencephalopathy with axonal spheroids and pigmented glia

Hayer

Santhanakumaran

Böhringer

et al. 2022

Ann Clin Transl Neurol

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Adult-onset leukoencephalopathy with axonal spheroids and pigmented glia (ALSP) leads to rapidly progressive dementia and is caused by mutations in the gene CSF1R. Neurodegeneration is driven by dysfunction of microglia, the predominant cell type expressing CSF1R in the brain. We assessed chitotriosidase, an enzyme secreted by microglia, in serum and cerebrospinal fluid of patients with ALSP. Chitotriosidase activity was highly increased in cerebrospinal fluid of patients and correlated inversely with disease duration. Of interest, presymptomatic CSF1R mutation carriers did not show elevated chitotriosidase levels. This makes chitotriosidase a promising new biomarker of disease activity for this rare disease.

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Chitotriosidase and lysosomal enzymes as potential biomarkers of disease progression in amyotrophic lateral sclerosis: A survey clinic-based study

Cited by 37 publications

References 33 publications

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

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

Evaluation of Chitotriosidase and CC-Chemokine Ligand 18 as Biomarkers of Microglia Activation in Amyotrophic Lateral Sclerosis

Chitotriosidase is a biomarker for adult‐onset leukoencephalopathy with axonal spheroids and pigmented glia

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