Plasma Cystatin C Correlates with Plasma NfL Levels and Predicts Disease Progression in Parkinson's Disease

Alberto Imarisio; Andrea Pilotto; Emirena Garrafa; Francesca Conforti; Stefano Masciocchi; Rosanna Turrone; Stefano Gipponi; Elisabetta Cottini; Maria Cristina Rizzetti; Vanessa Porrini; Cristina Gussago; Marina Pizzi; Fiorella Guadagni; Henrik Zetterberg; Nicholas J. Ashton; Abdul Hye; Alessandro Padovani

doi:10.1159/000523982

Plasma Cystatin C Correlates with Plasma NfL Levels and Predicts Disease Progression in Parkinson's Disease

Alberto Imarisio, Andrea Pilotto^*, Emirena Garrafa, Francesca Conforti, Stefano Masciocchi, Rosanna Turrone, Stefano Gipponi, Elisabetta Cottini, Maria Cristina Rizzetti, Vanessa Porrini, Cristina Gussago, Marina Pizzi, Fiorella Guadagni, Henrik Zetterberg, Nicholas J. Ashton, Abdul Hye, Alessandro Padovani

^*Corresponding author for this work

Research output: Contribution to journal › Article › peer-review

2 Citations (Scopus)

Abstract

Introduction: Previous studies reported increased plasma levels of cystatin C (Cys-C) in Parkinson's disease (PD) and claimed for a possible association with disease severity and progression. The aim of this study was to evaluate plasma Cys-C in PD and healthy controls (HC) and test its association with markers of peripheral inflammation, neurodegeneration, and clinical progression in a longitudinal study. Methods: Plasma Cys-C, high-sensitive C-reactive protein, interleukin 6, and neurofilament light chain (NfL) were assessed at the baseline in 71 consecutive non-demented PD and 69 HC. PD patients underwent an extensive motor and cognitive assessment at baseline and after 2 years of follow-up. The association of Cys-C with disease severity was evaluated in a multilinear model adjusted for the effect of age, sex, disease duration, and peripheral inflammation. Results: Cys-C levels appeared to be higher in PD compared to controls and correlated with the plasma neuronal marker NfL (r = 0.204, p = 0.046). In longitudinal analyses, PD patients with higher Cys-C levels exhibited faster motor progression at 2 years of follow-up independently from the peripheral inflammatory profile. Conclusions: Cys-C was associated with higher NfL levels and a remarkably faster motor progression in PD independently from peripheral inflammation. Further studies are needed in order to understand the mechanisms underpinning the association of Cys-C with higher neuronal damage markers in neurodegenerative diseases.

Original language	English
Pages (from-to)	109-116
Number of pages	8
Journal	Neurodegenerative Diseases
Volume	21
Issue number	5-6
DOIs	https://doi.org/10.1159/000523982
Publication status	Published - 1 Jul 2022

Keywords

Biomarkers
Cystatin-C
Neurofilament light chain
Parkinson's disease
Progression

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10.1159/000523982

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Imarisio, A., Pilotto, A., Garrafa, E., Conforti, F., Masciocchi, S., Turrone, R., Gipponi, S., Cottini, E., Rizzetti, M. C., Porrini, V., Gussago, C., Pizzi, M., Guadagni, F., Zetterberg, H., Ashton, N. J., Hye, A., & Padovani, A. (2022). Plasma Cystatin C Correlates with Plasma NfL Levels and Predicts Disease Progression in Parkinson's Disease. Neurodegenerative Diseases, 21(5-6), 109-116. https://doi.org/10.1159/000523982

@article{cc207aae50f646d5b008a55b3669beef,

title = "Plasma Cystatin C Correlates with Plasma NfL Levels and Predicts Disease Progression in Parkinson's Disease",

abstract = "Introduction: Previous studies reported increased plasma levels of cystatin C (Cys-C) in Parkinson's disease (PD) and claimed for a possible association with disease severity and progression. The aim of this study was to evaluate plasma Cys-C in PD and healthy controls (HC) and test its association with markers of peripheral inflammation, neurodegeneration, and clinical progression in a longitudinal study. Methods: Plasma Cys-C, high-sensitive C-reactive protein, interleukin 6, and neurofilament light chain (NfL) were assessed at the baseline in 71 consecutive non-demented PD and 69 HC. PD patients underwent an extensive motor and cognitive assessment at baseline and after 2 years of follow-up. The association of Cys-C with disease severity was evaluated in a multilinear model adjusted for the effect of age, sex, disease duration, and peripheral inflammation. Results: Cys-C levels appeared to be higher in PD compared to controls and correlated with the plasma neuronal marker NfL (r = 0.204, p = 0.046). In longitudinal analyses, PD patients with higher Cys-C levels exhibited faster motor progression at 2 years of follow-up independently from the peripheral inflammatory profile. Conclusions: Cys-C was associated with higher NfL levels and a remarkably faster motor progression in PD independently from peripheral inflammation. Further studies are needed in order to understand the mechanisms underpinning the association of Cys-C with higher neuronal damage markers in neurodegenerative diseases. ",

keywords = "Biomarkers, Cystatin-C, Neurofilament light chain, Parkinson's disease, Progression",

author = "Alberto Imarisio and Andrea Pilotto and Emirena Garrafa and Francesca Conforti and Stefano Masciocchi and Rosanna Turrone and Stefano Gipponi and Elisabetta Cottini and Rizzetti, {Maria Cristina} and Vanessa Porrini and Cristina Gussago and Marina Pizzi and Fiorella Guadagni and Henrik Zetterberg and Ashton, {Nicholas J.} and Abdul Hye and Alessandro Padovani",

note = "Funding Information: The recruitment of patients was partially supported by BIOMANE Project from the Health and Wealth research grants 2016 of the University of Brescia (Grant No. NP 1471, DMA) and MIUR PON “Ricerca e Innovazione” PerMedNet – project ARS01_01226. Publisher Copyright: {\textcopyright} 2022 ",

year = "2022",

month = jul,

day = "1",

doi = "10.1159/000523982",

language = "English",

volume = "21",

pages = "109--116",

journal = "Neurodegenerative Diseases",

issn = "1660-2854",

publisher = "Karger Publishers",

number = "5-6",

}

Imarisio, A, Pilotto, A, Garrafa, E, Conforti, F, Masciocchi, S, Turrone, R, Gipponi, S, Cottini, E, Rizzetti, MC, Porrini, V, Gussago, C, Pizzi, M, Guadagni, F, Zetterberg, H, Ashton, NJ , Hye, A & Padovani, A 2022, 'Plasma Cystatin C Correlates with Plasma NfL Levels and Predicts Disease Progression in Parkinson's Disease', Neurodegenerative Diseases, vol. 21, no. 5-6, pp. 109-116. https://doi.org/10.1159/000523982

TY - JOUR

T1 - Plasma Cystatin C Correlates with Plasma NfL Levels and Predicts Disease Progression in Parkinson's Disease

AU - Imarisio, Alberto

AU - Pilotto, Andrea

AU - Garrafa, Emirena

AU - Conforti, Francesca

AU - Masciocchi, Stefano

AU - Turrone, Rosanna

AU - Gipponi, Stefano

AU - Cottini, Elisabetta

AU - Rizzetti, Maria Cristina

AU - Porrini, Vanessa

AU - Gussago, Cristina

AU - Pizzi, Marina

AU - Guadagni, Fiorella

AU - Zetterberg, Henrik

AU - Ashton, Nicholas J.

AU - Hye, Abdul

AU - Padovani, Alessandro

N1 - Funding Information: The recruitment of patients was partially supported by BIOMANE Project from the Health and Wealth research grants 2016 of the University of Brescia (Grant No. NP 1471, DMA) and MIUR PON “Ricerca e Innovazione” PerMedNet – project ARS01_01226. Publisher Copyright: © 2022

PY - 2022/7/1

Y1 - 2022/7/1

N2 - Introduction: Previous studies reported increased plasma levels of cystatin C (Cys-C) in Parkinson's disease (PD) and claimed for a possible association with disease severity and progression. The aim of this study was to evaluate plasma Cys-C in PD and healthy controls (HC) and test its association with markers of peripheral inflammation, neurodegeneration, and clinical progression in a longitudinal study. Methods: Plasma Cys-C, high-sensitive C-reactive protein, interleukin 6, and neurofilament light chain (NfL) were assessed at the baseline in 71 consecutive non-demented PD and 69 HC. PD patients underwent an extensive motor and cognitive assessment at baseline and after 2 years of follow-up. The association of Cys-C with disease severity was evaluated in a multilinear model adjusted for the effect of age, sex, disease duration, and peripheral inflammation. Results: Cys-C levels appeared to be higher in PD compared to controls and correlated with the plasma neuronal marker NfL (r = 0.204, p = 0.046). In longitudinal analyses, PD patients with higher Cys-C levels exhibited faster motor progression at 2 years of follow-up independently from the peripheral inflammatory profile. Conclusions: Cys-C was associated with higher NfL levels and a remarkably faster motor progression in PD independently from peripheral inflammation. Further studies are needed in order to understand the mechanisms underpinning the association of Cys-C with higher neuronal damage markers in neurodegenerative diseases.

AB - Introduction: Previous studies reported increased plasma levels of cystatin C (Cys-C) in Parkinson's disease (PD) and claimed for a possible association with disease severity and progression. The aim of this study was to evaluate plasma Cys-C in PD and healthy controls (HC) and test its association with markers of peripheral inflammation, neurodegeneration, and clinical progression in a longitudinal study. Methods: Plasma Cys-C, high-sensitive C-reactive protein, interleukin 6, and neurofilament light chain (NfL) were assessed at the baseline in 71 consecutive non-demented PD and 69 HC. PD patients underwent an extensive motor and cognitive assessment at baseline and after 2 years of follow-up. The association of Cys-C with disease severity was evaluated in a multilinear model adjusted for the effect of age, sex, disease duration, and peripheral inflammation. Results: Cys-C levels appeared to be higher in PD compared to controls and correlated with the plasma neuronal marker NfL (r = 0.204, p = 0.046). In longitudinal analyses, PD patients with higher Cys-C levels exhibited faster motor progression at 2 years of follow-up independently from the peripheral inflammatory profile. Conclusions: Cys-C was associated with higher NfL levels and a remarkably faster motor progression in PD independently from peripheral inflammation. Further studies are needed in order to understand the mechanisms underpinning the association of Cys-C with higher neuronal damage markers in neurodegenerative diseases.

KW - Biomarkers

KW - Cystatin-C

KW - Neurofilament light chain

KW - Parkinson's disease

KW - Progression

UR - http://www.scopus.com/inward/record.url?scp=85134721477&partnerID=8YFLogxK

U2 - 10.1159/000523982

DO - 10.1159/000523982

M3 - Article

C2 - 35287127

AN - SCOPUS:85134721477

SN - 1660-2854

VL - 21

SP - 109

EP - 116

JO - Neurodegenerative Diseases

JF - Neurodegenerative Diseases

IS - 5-6

ER -

Plasma Cystatin C Correlates with Plasma NfL Levels and Predicts Disease Progression in Parkinson's Disease

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