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Targeted discovery and validation of plasma biomarkers of Parkinson's disease.
J Proteome Res. 2014 Nov 07; 13(11):4535-45.JP

Abstract

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.

Authors+Show Affiliations

Department of Pathology, University of Washington School of Medicine , 325 9th Avenue, HMC 359635, Seattle, Washington 98104, United States.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, N.I.H., Extramural
Validation Study

Language

eng

PubMed ID

24853996

Citation

Pan, Catherine, et al. "Targeted Discovery and Validation of Plasma Biomarkers of Parkinson's Disease." Journal of Proteome Research, vol. 13, no. 11, 2014, pp. 4535-45.
Pan C, Zhou Y, Dator R, et al. Targeted discovery and validation of plasma biomarkers of Parkinson's disease. J Proteome Res. 2014;13(11):4535-45.
Pan, C., Zhou, Y., Dator, R., Ginghina, C., Zhao, Y., Movius, J., Peskind, E., Zabetian, C. P., Quinn, J., Galasko, D., Stewart, T., Shi, M., & Zhang, J. (2014). Targeted discovery and validation of plasma biomarkers of Parkinson's disease. Journal of Proteome Research, 13(11), 4535-45. https://doi.org/10.1021/pr500421v
Pan C, et al. Targeted Discovery and Validation of Plasma Biomarkers of Parkinson's Disease. J Proteome Res. 2014 Nov 7;13(11):4535-45. PubMed PMID: 24853996.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Targeted discovery and validation of plasma biomarkers of Parkinson's disease. AU - Pan,Catherine, AU - Zhou,Yong, AU - Dator,Romel, AU - Ginghina,Carmen, AU - Zhao,Yanchun, AU - Movius,James, AU - Peskind,Elaine, AU - Zabetian,Cyrus P, AU - Quinn,Joseph, AU - Galasko,Douglas, AU - Stewart,Tessandra, AU - Shi,Min, AU - Zhang,Jing, Y1 - 2014/06/11/ PY - 2014/5/24/entrez PY - 2014/5/24/pubmed PY - 2015/7/15/medline KW - Parkinson’s disease KW - peripheral biomarkers KW - selected reaction monitoring KW - targeted mass spectrometry SP - 4535 EP - 45 JF - Journal of proteome research JO - J Proteome Res VL - 13 IS - 11 N2 - 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. SN - 1535-3907 UR - https://www.unboundmedicine.com/medline/citation/24853996/Targeted_discovery_and_validation_of_plasma_biomarkers_of_Parkinson's_disease_ L2 - https://doi.org/10.1021/pr500421v DB - PRIME DP - Unbound Medicine ER -