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Targeted Discovery and Validation of Plasma Biomarkers of Parkinson’s Disease

[Image: see text] Despite extensive research, an unmet need remains for protein biomarkers of Parkinson’s disease (PD) in peripheral body fluids, especially blood, which is easily accessible clinically. The discovery of such biomarkers is challenging, however, due to the enormous complexity and huge...

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Autores principales: Pan, Catherine, Zhou, Yong, Dator, Romel, Ginghina, Carmen, Zhao, Yanchun, Movius, James, Peskind, Elaine, Zabetian, Cyrus P., Quinn, Joseph, Galasko, Douglas, Stewart, Tessandra, Shi, Min, Zhang, Jing
Formato: Online Artículo Texto
Lenguaje:English
Publicado: American Chemical Society 2014
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4224986/
https://www.ncbi.nlm.nih.gov/pubmed/24853996
http://dx.doi.org/10.1021/pr500421v
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author Pan, Catherine
Zhou, Yong
Dator, Romel
Ginghina, Carmen
Zhao, Yanchun
Movius, James
Peskind, Elaine
Zabetian, Cyrus P.
Quinn, Joseph
Galasko, Douglas
Stewart, Tessandra
Shi, Min
Zhang, Jing
author_facet Pan, Catherine
Zhou, Yong
Dator, Romel
Ginghina, Carmen
Zhao, Yanchun
Movius, James
Peskind, Elaine
Zabetian, Cyrus P.
Quinn, Joseph
Galasko, Douglas
Stewart, Tessandra
Shi, Min
Zhang, Jing
author_sort Pan, Catherine
collection PubMed
description [Image: see text] Despite extensive research, an unmet need remains for protein biomarkers of Parkinson’s disease (PD) in peripheral body fluids, especially blood, which is easily accessible clinically. The discovery of such biomarkers is challenging, however, due to the enormous complexity and huge dynamic range of human blood proteins, which are derived from nearly all organ systems, with those originating specifically from the central nervous system (CNS) being exceptionally low in abundance. In this investigation of a relatively large cohort (∼300 subjects), selected reaction monitoring (SRM) assays (a targeted approach) were used to probe plasma peptides derived from glycoproteins previously found to be altered in the CNS based on PD diagnosis or severity. Next, the detected peptides were interrogated for their diagnostic sensitivity and specificity as well as the correlation with PD severity, as determined by the Unified Parkinson’s Disease Rating Scale (UPDRS). The results revealed that 12 of the 50 candidate glycopeptides were reliably and consistently identified in plasma samples, with three of them displaying significant differences among diagnostic groups. A combination of four peptides (derived from PRNP, HSPG2, MEGF8, and NCAM1) provided an overall area under curve (AUC) of 0.753 (sensitivity: 90.4%; specificity: 50.0%). Additionally, combining two peptides (derived from MEGF8 and ICAM1) yielded significant correlation with PD severity, that is, UPDRS (r = 0.293, p = 0.004). The significance of these results is at least two-fold: (1) it is possible to use a targeted approach to identify otherwise very difficult to detect CNS related biomarkers in peripheral blood and (2) the novel biomarkers, if validated in independent cohorts, can be employed to assist with clinical diagnosis of PD as well as monitoring disease progression.
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spelling pubmed-42249862015-05-22 Targeted Discovery and Validation of Plasma Biomarkers of Parkinson’s Disease Pan, Catherine Zhou, Yong Dator, Romel Ginghina, Carmen Zhao, Yanchun Movius, James Peskind, Elaine Zabetian, Cyrus P. Quinn, Joseph Galasko, Douglas Stewart, Tessandra Shi, Min Zhang, Jing J Proteome Res [Image: see text] Despite extensive research, an unmet need remains for protein biomarkers of Parkinson’s disease (PD) in peripheral body fluids, especially blood, which is easily accessible clinically. The discovery of such biomarkers is challenging, however, due to the enormous complexity and huge dynamic range of human blood proteins, which are derived from nearly all organ systems, with those originating specifically from the central nervous system (CNS) being exceptionally low in abundance. In this investigation of a relatively large cohort (∼300 subjects), selected reaction monitoring (SRM) assays (a targeted approach) were used to probe plasma peptides derived from glycoproteins previously found to be altered in the CNS based on PD diagnosis or severity. Next, the detected peptides were interrogated for their diagnostic sensitivity and specificity as well as the correlation with PD severity, as determined by the Unified Parkinson’s Disease Rating Scale (UPDRS). The results revealed that 12 of the 50 candidate glycopeptides were reliably and consistently identified in plasma samples, with three of them displaying significant differences among diagnostic groups. A combination of four peptides (derived from PRNP, HSPG2, MEGF8, and NCAM1) provided an overall area under curve (AUC) of 0.753 (sensitivity: 90.4%; specificity: 50.0%). Additionally, combining two peptides (derived from MEGF8 and ICAM1) yielded significant correlation with PD severity, that is, UPDRS (r = 0.293, p = 0.004). The significance of these results is at least two-fold: (1) it is possible to use a targeted approach to identify otherwise very difficult to detect CNS related biomarkers in peripheral blood and (2) the novel biomarkers, if validated in independent cohorts, can be employed to assist with clinical diagnosis of PD as well as monitoring disease progression. American Chemical Society 2014-05-22 2014-11-07 /pmc/articles/PMC4224986/ /pubmed/24853996 http://dx.doi.org/10.1021/pr500421v Text en Copyright © 2014 American Chemical Society This is an open access article published under an ACS AuthorChoice License (http://pubs.acs.org/page/policy/authorchoice_termsofuse.html) , which permits copying and redistribution of the article or any adaptations for non-commercial purposes.
spellingShingle Pan, Catherine
Zhou, Yong
Dator, Romel
Ginghina, Carmen
Zhao, Yanchun
Movius, James
Peskind, Elaine
Zabetian, Cyrus P.
Quinn, Joseph
Galasko, Douglas
Stewart, Tessandra
Shi, Min
Zhang, Jing
Targeted Discovery and Validation of Plasma Biomarkers of Parkinson’s Disease
title Targeted Discovery and Validation of Plasma Biomarkers of Parkinson’s Disease
title_full Targeted Discovery and Validation of Plasma Biomarkers of Parkinson’s Disease
title_fullStr Targeted Discovery and Validation of Plasma Biomarkers of Parkinson’s Disease
title_full_unstemmed Targeted Discovery and Validation of Plasma Biomarkers of Parkinson’s Disease
title_short Targeted Discovery and Validation of Plasma Biomarkers of Parkinson’s Disease
title_sort targeted discovery and validation of plasma biomarkers of parkinson’s disease
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4224986/
https://www.ncbi.nlm.nih.gov/pubmed/24853996
http://dx.doi.org/10.1021/pr500421v
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