Cerebrospinal fluid proteomics implicates the granin family in Parkinson’s disease
Open accessAbstract
Parkinson’s disease, the most common age-related movement disorder, is a progressive neurodegenerative disease with unclear etiology. Better understanding of the underlying disease mechanism(s) is an urgent need for the development of disease-modifying therapeutics. Limited studies have been performed in large patient cohorts to identify protein alterations in cerebrospinal fluid (CSF), a proximal site to pathology. We set out to identify disease-relevant protein changes in CSF to gain insights into the etiology of Parkinson’s disease and potentially assist in disease biomarker identification. In this study, we used liquid chromatography-tandem mass spectrometry in data-independent acquisition (DIA) mode to identify Parkinson’s-relevant biomarkers in cerebrospinal fluid. We quantified 341 protein groups in two independent cohorts (n = 196) and a longitudinal cohort (n = 105 samples, representing 40 patients) consisting of Parkinson’s disease and healthy control samples from three different sources. A first cohort of 53 Parkinson’s disease and 72 control samples was analyzed, identifying 53 proteins with significant changes (p < 0.05) in Parkinson’s disease relative to healthy control. We established a biomarker signature and multiple protein ratios that differentiate Parkinson’s disease from healthy controls and validated these results in an independent cohort. The second cohort included 28 Parkinson’s disease and 43 control samples. Independent analysis of these samples identified 41 proteins with significant changes. Evaluation of the overlapping changes between the two cohorts identified 13 proteins with consistent and significant changes (p < 0.05). Importantly, we found the extended granin family proteins as reduced in disease, suggesting a potential common mechanism for the biological reduction in monoamine neurotransmission in Parkinson’s patients. Our study identifies several novel protein changes in Parkinson’s disease cerebrospinal fluid that may be exploited for understanding etiology of disease and for biomarker development.
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Peptides in the C-terminal or N-terminal regions of granin family proteins were found to be decreased in Parkinson's disease.
“Specifically, peptides in the C-terminal or N-terminal regions of granin family proteins were found to be decreased in Parkinson’s.(20)”
From Putting humpty dumpty back together again: what does protein quantification mean in bottom-up proteomics? (2022) · cites this paper as [20]
A study of cerebrospinal fluid in Parkinson's disease found specific tryptic peptides differentially abundant in affected individuals compared with healthy age-matched controls.
“For example, a study of cerebrospinal fluid in Parkinson’s disease found that specific tryptic peptides are differentially abundant in affected individuals compared to healthy, age-matched controls.”
From Putting humpty dumpty back together again: what does protein quantification mean in bottom-up proteomics? (2022) · cites this paper as [20]
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- Authors
- Rotunno, M. S., Lane, M., Zhang, W., Wolf, P., Oliva, P., Viel, C., Wills, A.-M., Alcalay, R. N., Scherzer, C. R., Shihabuddin, L. S., Zhang, K., & Sardi, S. P.
- Affiliations
- Sanofi (United States) (US)
- Massachusetts General Hospital (US)
- Columbia University (US)
- Brigham and Women's Hospital (US)
- Corresponding author
- Sardi, S. Pablo
- ORCID
- Venue
- Scientific Reports
- Published
- 2020-02-12
- Volume
- 10
- Issue
- 1
- Pages
- 2479-2479
- ISSN
- 2045-2322 (ISSN-L)
- PMC
- PMC7015906
- OpenAlex
- W3005908769
- Cited by
- 94
- References
- 61
- Citations by year
- 2026: 8 · 2025: 12 · 2024: 13 · 2023: 16 · 2022: 24 · 2021: 18 · 2020: 3
- FWCI
- 6.60
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Locations
- Scientific Reports (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- Funders
- Michael J. Fox Foundation for Parkinson's Research
- Harvard NeuroDiscovery Center
- Brigham and Women's Hospital
- Massachusetts General Hospital
- National Institutes of Health
- National Institute on Aging (R01 AG057331, RF1AG057331, P50AG005134, R01AG005731)
- National Institute of Neurological Disorders and Stroke (U01NS082157, U01NS100603, U01NS095736)
- Topics
- Health Sciences › Medicine › Neurology › Parkinson's Disease Mechanisms and Treatments
- Physical Sciences › Chemistry › Spectroscopy › Advanced Proteomics Techniques and Applications
- Health Sciences › Medicine › Neurology › Neurological disorders and treatments
- Keywords
- Parkinson's disease, cerebrospinal fluid proteomics, biomarkers, disease-modifying therapy, monoamine neurotransmission, neurodegeneration, protein ratio, biomarker signatures
- MeSH terms
- Aged, Chromogranins, Female, Humans, Male, Middle Aged, Parkinson Disease, Biomarkers, Proteomics, Tandem Mass Spectrometry
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