Cystatin C Secretion in Blood Derivatives and Cellular Models of Idiopathic Parkinson’s Disease

Parkinson’s disease is an age-related progressive neurodegenerative disorder. A large majority of Parkinson’s disease patients have an unknown etiology, which is classified as idiopathic Parkinson’s disease. Generating disease models directly from idiopathic Parkinson’s disease patients may improve...

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Main Authors: Kathleen Mommaerts, Anna S. Monzel, Alise Zagare, Sarah L. Nickels, Nico J. Diederich, Laura Longhino, William Mathieson, Paul M. A. Antony, Fay Betsou, Jens C. Schwamborn
Format: Article
Language:English
Published: Wiley 2025-01-01
Series:Parkinson's Disease
Online Access:http://dx.doi.org/10.1155/padi/5149071
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author Kathleen Mommaerts
Anna S. Monzel
Alise Zagare
Sarah L. Nickels
Nico J. Diederich
Laura Longhino
William Mathieson
Paul M. A. Antony
Fay Betsou
Jens C. Schwamborn
author_facet Kathleen Mommaerts
Anna S. Monzel
Alise Zagare
Sarah L. Nickels
Nico J. Diederich
Laura Longhino
William Mathieson
Paul M. A. Antony
Fay Betsou
Jens C. Schwamborn
author_sort Kathleen Mommaerts
collection DOAJ
description Parkinson’s disease is an age-related progressive neurodegenerative disorder. A large majority of Parkinson’s disease patients have an unknown etiology, which is classified as idiopathic Parkinson’s disease. Generating disease models directly from idiopathic Parkinson’s disease patients may improve the understanding of the disease pathology. Both neuroprotective and neurodegenerative roles have been suggested for cystatin C in neurodegenerative disease. In Parkinson’s disease, investigations assessing cystatin C levels in different types of biospecimens such as blood, cerebrospinal fluid, and in vitro models have had conflicting results. We present a study assessing cystatin C levels in different biospecimen types originating from the same subjects. Using a sandwich ELISA, we compared cystatin C concentration in blood derivatives (plasma and serum) and culture media of derived models (stem cells, neuroepithelial stem cells, and midbrain organoids) of three idiopathic Parkinson’s disease and three age-matched healthy control subjects with the same CST3 genotype. Genotyping analyses confirmed that all subjects were homozygous AA. The identity of the derived models was confirmed using immunohistochemical staining. Secreted cystatin C concentration was measured in each biospecimen tested. No statistically significant differences in cystatin C concentrations were found between the subjects in any of the biospecimen types. As a personalized marker, a higher cystatin C concentration was shown for some individual patients in the culture medium of midbrain organoids, suggesting a potential involvement in Parkinson’s disease physiopathology. This proof of concept demonstrates that cystatin C is secreted by various idiopathic Parkinson’s disease cell models, including midbrain organoids, which in turn suggests that cystatin C secretion by midbrain organoids might be pertinent in neurodegenerative disease research.
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spelling doaj-art-dbad2eb1b68448e88cf5931b0df71c472025-02-01T00:00:05ZengWileyParkinson's Disease2042-00802025-01-01202510.1155/padi/5149071Cystatin C Secretion in Blood Derivatives and Cellular Models of Idiopathic Parkinson’s DiseaseKathleen Mommaerts0Anna S. Monzel1Alise Zagare2Sarah L. Nickels3Nico J. Diederich4Laura Longhino5William Mathieson6Paul M. A. Antony7Fay Betsou8Jens C. Schwamborn9Integrated Biobank of LuxembourgLuxembourg Centre for Systems BiomedicineLuxembourg Centre for Systems BiomedicineLuxembourg Centre for Systems BiomedicineDepartment of NeurosciencesDepartment of NeurosciencesIntegrated Biobank of LuxembourgLuxembourg Centre for Systems BiomedicineCentre de Ressources Biologiques de l’Institut PasteurLuxembourg Centre for Systems BiomedicineParkinson’s disease is an age-related progressive neurodegenerative disorder. A large majority of Parkinson’s disease patients have an unknown etiology, which is classified as idiopathic Parkinson’s disease. Generating disease models directly from idiopathic Parkinson’s disease patients may improve the understanding of the disease pathology. Both neuroprotective and neurodegenerative roles have been suggested for cystatin C in neurodegenerative disease. In Parkinson’s disease, investigations assessing cystatin C levels in different types of biospecimens such as blood, cerebrospinal fluid, and in vitro models have had conflicting results. We present a study assessing cystatin C levels in different biospecimen types originating from the same subjects. Using a sandwich ELISA, we compared cystatin C concentration in blood derivatives (plasma and serum) and culture media of derived models (stem cells, neuroepithelial stem cells, and midbrain organoids) of three idiopathic Parkinson’s disease and three age-matched healthy control subjects with the same CST3 genotype. Genotyping analyses confirmed that all subjects were homozygous AA. The identity of the derived models was confirmed using immunohistochemical staining. Secreted cystatin C concentration was measured in each biospecimen tested. No statistically significant differences in cystatin C concentrations were found between the subjects in any of the biospecimen types. As a personalized marker, a higher cystatin C concentration was shown for some individual patients in the culture medium of midbrain organoids, suggesting a potential involvement in Parkinson’s disease physiopathology. This proof of concept demonstrates that cystatin C is secreted by various idiopathic Parkinson’s disease cell models, including midbrain organoids, which in turn suggests that cystatin C secretion by midbrain organoids might be pertinent in neurodegenerative disease research.http://dx.doi.org/10.1155/padi/5149071
spellingShingle Kathleen Mommaerts
Anna S. Monzel
Alise Zagare
Sarah L. Nickels
Nico J. Diederich
Laura Longhino
William Mathieson
Paul M. A. Antony
Fay Betsou
Jens C. Schwamborn
Cystatin C Secretion in Blood Derivatives and Cellular Models of Idiopathic Parkinson’s Disease
Parkinson's Disease
title Cystatin C Secretion in Blood Derivatives and Cellular Models of Idiopathic Parkinson’s Disease
title_full Cystatin C Secretion in Blood Derivatives and Cellular Models of Idiopathic Parkinson’s Disease
title_fullStr Cystatin C Secretion in Blood Derivatives and Cellular Models of Idiopathic Parkinson’s Disease
title_full_unstemmed Cystatin C Secretion in Blood Derivatives and Cellular Models of Idiopathic Parkinson’s Disease
title_short Cystatin C Secretion in Blood Derivatives and Cellular Models of Idiopathic Parkinson’s Disease
title_sort cystatin c secretion in blood derivatives and cellular models of idiopathic parkinson s disease
url http://dx.doi.org/10.1155/padi/5149071
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