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Molecular markers of early Parkinson's disease based on gene expression in blood.
Proc Natl Acad Sci U S A. 2007 Jan 16; 104(3):955-60.PN

Abstract

Parkinson's disease (PD) progresses relentlessly and affects five million people worldwide. Laboratory tests for PD are critically needed for developing treatments designed to slow or prevent progression of the disease. We performed a transcriptome-wide scan in 105 individuals to interrogate the molecular processes perturbed in cellular blood of patients with early-stage PD. The molecular multigene marker here identified is associated with risk of PD in 66 samples of the training set comprising healthy and disease controls [third tertile cross-validated odds ratio of 5.7 (P for trend 0.005)]. It is further validated in 39 independent test samples [third tertile odds ratio of 5.1 (P for trend 0.04)]. Insights into disease-linked processes detectable in peripheral blood are offered by 22 unique genes differentially expressed in patients with PD versus healthy individuals. These include the co-chaperone ST13, which stabilizes heat-shock protein 70, a modifier of alpha-synuclein misfolding and toxicity. ST13 messenger RNA copies are lower in patients with PD (mean +/- SE 0.59 +/- 0.05) than in controls (0.96 +/- 0.09) (P = 0.002) in two independent populations. Thus, gene expression signals measured in blood can facilitate the development of biomarkers for PD.

Authors+Show Affiliations

Center for Neurologic Diseases, Brigham and Women's Hospital and Harvard Medical School, 65 Landsdowne Street, Cambridge, MA 02139, USA. cscherzer@rics.bwh.harvard.eduNo 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 availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

17215369

Citation

Scherzer, Clemens R., et al. "Molecular Markers of Early Parkinson's Disease Based On Gene Expression in Blood." Proceedings of the National Academy of Sciences of the United States of America, vol. 104, no. 3, 2007, pp. 955-60.
Scherzer CR, Eklund AC, Morse LJ, et al. Molecular markers of early Parkinson's disease based on gene expression in blood. Proc Natl Acad Sci U S A. 2007;104(3):955-60.
Scherzer, C. R., Eklund, A. C., Morse, L. J., Liao, Z., Locascio, J. J., Fefer, D., Schwarzschild, M. A., Schlossmacher, M. G., Hauser, M. A., Vance, J. M., Sudarsky, L. R., Standaert, D. G., Growdon, J. H., Jensen, R. V., & Gullans, S. R. (2007). Molecular markers of early Parkinson's disease based on gene expression in blood. Proceedings of the National Academy of Sciences of the United States of America, 104(3), 955-60.
Scherzer CR, et al. Molecular Markers of Early Parkinson's Disease Based On Gene Expression in Blood. Proc Natl Acad Sci U S A. 2007 Jan 16;104(3):955-60. PubMed PMID: 17215369.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Molecular markers of early Parkinson's disease based on gene expression in blood. AU - Scherzer,Clemens R, AU - Eklund,Aron C, AU - Morse,Lee J, AU - Liao,Zhixiang, AU - Locascio,Joseph J, AU - Fefer,Daniel, AU - Schwarzschild,Michael A, AU - Schlossmacher,Michael G, AU - Hauser,Michael A, AU - Vance,Jeffery M, AU - Sudarsky,Lewis R, AU - Standaert,David G, AU - Growdon,John H, AU - Jensen,Roderick V, AU - Gullans,Steven R, Y1 - 2007/01/10/ PY - 2007/1/12/pubmed PY - 2007/2/28/medline PY - 2007/1/12/entrez SP - 955 EP - 60 JF - Proceedings of the National Academy of Sciences of the United States of America JO - Proc Natl Acad Sci U S A VL - 104 IS - 3 N2 - Parkinson's disease (PD) progresses relentlessly and affects five million people worldwide. Laboratory tests for PD are critically needed for developing treatments designed to slow or prevent progression of the disease. We performed a transcriptome-wide scan in 105 individuals to interrogate the molecular processes perturbed in cellular blood of patients with early-stage PD. The molecular multigene marker here identified is associated with risk of PD in 66 samples of the training set comprising healthy and disease controls [third tertile cross-validated odds ratio of 5.7 (P for trend 0.005)]. It is further validated in 39 independent test samples [third tertile odds ratio of 5.1 (P for trend 0.04)]. Insights into disease-linked processes detectable in peripheral blood are offered by 22 unique genes differentially expressed in patients with PD versus healthy individuals. These include the co-chaperone ST13, which stabilizes heat-shock protein 70, a modifier of alpha-synuclein misfolding and toxicity. ST13 messenger RNA copies are lower in patients with PD (mean +/- SE 0.59 +/- 0.05) than in controls (0.96 +/- 0.09) (P = 0.002) in two independent populations. Thus, gene expression signals measured in blood can facilitate the development of biomarkers for PD. SN - 0027-8424 UR - https://www.unboundmedicine.com/medline/citation/17215369/Molecular_markers_of_early_Parkinson's_disease_based_on_gene_expression_in_blood_ L2 - http://www.pnas.org/cgi/pmidlookup?view=long&pmid=17215369 DB - PRIME DP - Unbound Medicine ER -