Cystatin <scp>C</scp> is differentially involved in multiple system atrophy phenotypes

Urbizu, Aintzane; Canet-Pons, Júlia; Muñoz-Mármol, Ana M; Aldecoa, Ibán; López, María Teresa Rugeles; Compta, Yaroslau; Álvarez, Ramiro; Ispierto, Lourdes; Tolosa, Eduardo; Ariza, Aurelio; Beyer, Katrin

doi:10.1111/nan.12134

Cited by 8 publications

(7 citation statements)

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“…Both levels of Cys C in serum or CSF of AD patients have been shown to be lower 43 , 48 , 49 , and the Cys C levels in CSF is strong positively correlation with alteration of both tau and Aβ 42 levels in CSF 43 . High mRNA levels of Cys C were found in caudate nuclei and cerebella of MSA patients brain 50 and similar results were observed in the vitro and vivo model of Parkinson's disease 51 , 52 . Like AD, the levels of Cys C in CSF are seemingly decreased during disease progression in ALS patients and the reduced Cys C is negatively correlated with survival time 26 .…”

Section: Discussionsupporting

confidence: 83%

“…Several studies of relevant NDDs showed the reduced levels of Cys C in CSF or the increased expression of Cys C in degenerative neurons 18 , 48 , 49 , 50 , 51 . Both levels of Cys C in serum or CSF of AD patients have been shown to be lower 43 , 48 , 49 , and the Cys C levels in CSF is strong positively correlation with alteration of both tau and Aβ 42 levels in CSF 43 .…”

Section: Discussionmentioning

confidence: 99%

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Aberrant Levels of Cystatin C in Amyotrophic Lateral Sclerosis: a Systematic Review and Meta Analysis

Zhu

Yang

et al. 2018

Int. J. Biol. Sci.

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Evidences suggest that Cystatin C (Cys C) levels might be a biomarker in amyotrophic lateral sclerosis (ALS) diagnosis, but the conclusion is still in doubts. We conducted a systematic review and meta analysis of Cys C levels in cerebrospinal cord fluid (CSF) and peripheral blood of patients with ALS in order to further confirm whether or not Cys C levels is a biomarker in ALS diagnosis. The English relevant studies without year limitation were systematically searched in PubMed, EMBASE, Web of Science databases. The searched term contained "Amyotrophic Lateral Sclerosis" or "Motor Neuron Diseases" and "Cystatin C" and "Cerebrospinal fluid" or "CSF" or "Biomarker" or "Serum" or "Plasma" or "Blood". Observational studies reporting the associations between Cys C levels and ALS patients were selected to conduct a systematic review and meta analysis. Two reviewers performed the selection of this study independently. The Newcastle-Ottawa Scale assesses the quality and risk of bias of selected studies. Estimates were pooled using a random-effects model. The Cys C levels of CSF or peripheral blood in ALS patients compared with health controls (HCs) and several relevant neurodegenerative diseases (NDDs). Sixteen studies were included in our systematic review, 9 of them were selected to perform the meta analysis. Of these, eight studies measured Cys C levels in CSF and three studies measured it in blood. Cys C levels in CSF were significantly lower in ALS patients than in HCs (Hedge's g = -1.398, 95%CI: -2.43 to -0.36; p = 0.008), but there was no statistical difference between ALS patients and several relevant NDDs. No statistically significant difference in the Cys C levels of blood in the comparison between ALS and HCs. The correlation meta analysis presented no significant correlation between Cys C levels in CSF and age or disease duration respectively. Cys C levels significantly decrease in the CSF of ALS patients, but are not a specific biomarker for this disease. Cys C levels in CSF might be an auxiliary diagnostic biomarker of ALS.

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Section: Discussionsupporting

confidence: 83%

Section: Discussionmentioning

confidence: 99%

Aberrant Levels of Cystatin C in Amyotrophic Lateral Sclerosis: a Systematic Review and Meta Analysis

Zhu

Yang

et al. 2018

Int. J. Biol. Sci.

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“…In a former study, Urbizu et al (2015) confirmed that the transcription of Cys-C was differentially expressed in different MSA phenotypes. The Cys-C gene (CST3) B-haplotype was significantly associated with MSA-P, while the higher expression of CST3 were found in the caudate nuclei of MSA-P and in the cerebellum of MSA-C.…”

Section: Discussionmentioning

confidence: 68%

Serum Cystatin C as a Potential Predictor of the Severity of Multiple System Atrophy With Predominant Cerebellar Ataxia: A Case-Control Study in Chinese Population

Wang

et al. 2021

Front. Neurosci.

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Objective: Multiple system atrophy (MSA) is a serious neurodegenerative disease that is charactered by progressive neurological disability. The aim of this study was to investigate the correlation of serum oxidant factors with the severity of MSA.Methods: A total of 52 MSA patients and 52 age- and gender- matched healthy subjects were retrospectively enrolled in this study. Enzymatic colorimetric methods were used to assay the concentrations of uric acid (UA), serum creatinine (Scr), blood urea nitrogen (BUN), and cystatin C (Cys-C). Disease severity was evaluated by the Unified Multiple System Atrophy Rating Scale (UMSARS). The disease progression rate was defined by the change in UMSARS-IV (global disability score, GDS) over a 1-year period.Results: Comparisons between the two groups revealed that there were no significant differences in terms of serum Scr (70.81 ± 13.88 vs. 70.92 ± 14.19 μmol/L, p = 0.967). However, the serum levels of the other three biomarkers were significantly higher in the MSA patients (UA: 325.31 ± 84.92 vs. 291.19 ± 64.14 μmol/L, p = 0.023; BUN: 5.68 ± 1.67 vs. 4.60 ± 1.24 mmol/L, p < 0.001; Cys-C: 0.96 ± 0.15 vs. 0.89 ± 0.14 mg/L, p = 0.024). In addition, Pearson correlation analyses revealed that only serum Cys-C was significantly correlated to GDS (r = 0.281, p = 0.044). Subgroup analysis further demonstrated that serum Cys-C was the only factor that was positively associated with the disease severity in patients with MSA and predominant cerebellar ataxia (MSA-C) (r = 0.444, p = 0.018); there was no significant association in MSA patients with predominant Parkinsonism (MSA-P) (r = 0.118, p = 0.582). MSA-C patients with severe disability were shown to express higher serum levels of Cys-C than patients with mild disability (1.03 ± 0.13 vs. 0.88 ± 0.12 mg/L, p = 0.009). Finally, Kaplan-Meier plots revealed a significant difference in the 5-year probability of survival from severe disability between MSA-C patients with high- and low-concentrations of serum Cys-C (Log-rank test: X2 = 4.154, p = 0.042). ROC curve analysis confirmed that serum Cys-C exhibits good performance as a biomarker (AUC = 0.847).Conclusion: Our research indicated that oxidative stress plays a vital role in MSA. Serum Cys-C represents a potential prognostic biomarker to evaluate the severity of disease in patients with MSA-C.

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“…Monoclonal and polyclonal antibodies against CPE were obtained from BD Biosciences (610758, BD Transduction Laboratories, San Jose, CA) and GeneTex (GTX23533, GeneTex Inc), respectively [ 45 , 46 ]. Polyclonal antibodies against CysC (ABC20) [ 47 ] and monoclonal antibodies against GFAP (MAB3402) were obtained from Millipore Iberica (Madrid, Spain). Monoclonal and polyclonal antibodies against CHMP2B (MAB7509) and CK1δ (AF4568) were purchased from R&D Systems (Minneapolis, MN).…”

Section: Methodsmentioning

confidence: 99%

Dense core vesicle markers in CSF and cortical tissues of patients with Alzheimer’s disease

Barranco

Plá

Alcolea

et al. 2021

Transl Neurodegener

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Background New fluid biomarkers for Alzheimer's disease (AD) that reveal synaptic and neural network dysfunctions are needed for clinical practice and therapeutic trial design. Dense core vesicle (DCV) cargos are promising cerebrospinal fluid (CSF) indicators of synaptic failure in AD patients. However, their value as biomarkers has not yet been determined. Methods Immunoassays were performed to analyze the secretory proteins prohormone convertases PC1/3 and PC2, carboxypeptidase E (CPE), secretogranins SgIII and SgII, and Cystatin C in the cerebral cortex (n = 45, provided by Bellvitge University Hospital) and CSF samples (n = 66, provided by The Sant Pau Initiative on Neurodegeneration cohort) from AD patients (n = 56) and age-matched controls (n = 55). Results In AD tissues, most DCV proteins were aberrantly accumulated in dystrophic neurites and activated astrocytes, whereas PC1/3, PC2 and CPE were also specifically accumulated in hippocampal granulovacuolar degeneration bodies. AD individuals displayed an overall decline of secretory proteins in the CSF. Interestingly, in AD patients, the CSF levels of prohormone convertases strongly correlated inversely with those of neurodegeneration markers and directly with cognitive impairment status. Conclusions These results demonstrate marked alterations of neuronal-specific prohormone convertases in CSF and cortical tissues of AD patients. The neuronal DCV cargos are biomarker candidates for synaptic dysfunction and neurodegeneration in AD.

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Cystatin C is differentially involved in multiple system atrophy phenotypes

Abstract: CysC changes are differentially present in the parkinsonian and cerebellar forms of MSA and may play an important role in the pathogenesis of this neurodegenerative condition.

Cited by 8 publications

References 50 publications

Aberrant Levels of Cystatin C in Amyotrophic Lateral Sclerosis: a Systematic Review and Meta Analysis

Aberrant Levels of Cystatin C in Amyotrophic Lateral Sclerosis: a Systematic Review and Meta Analysis

Serum Cystatin C as a Potential Predictor of the Severity of Multiple System Atrophy With Predominant Cerebellar Ataxia: A Case-Control Study in Chinese Population

Dense core vesicle markers in CSF and cortical tissues of patients with Alzheimer’s disease

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