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Pilot study: peripheral biomarkers for diagnosing sporadic Parkinson's disease.
J Neural Transm (Vienna). 2010 Dec; 117(12):1387-93.JN

Abstract

The need for an early and differential diagnosis of Parkinson's disease (PD) is undoubtedly one of the main quests of the century. An early biomarker would enable therapy to begin sooner and would, hopefully, slow or better prevent progression of the disease. We performed transcript profiling via quantitative RT-PCR in RNA originating from peripheral blood samples. The groups were de novo (n = 11) and medicated PD (n = 94) subjects and healthy controls (n = 34), while for negative control Alzheimer's disease (AD; n = 14) subjects were recruited as an additional neurodegenerative disease. The results were retested on a second recruitment consisting 22 medicated PD subjects versus 33 controls and 12 AD. Twelve transcripts were chosen as candidate genes, according to previous postmortem brain profiling. Multiple analyses resulted in four significant genes: proteasome (prosome, macropain) subunit-alpha type-2 (PSMA2; p = 0.0002, OR = 1.15 95% CI 1.07-1.24), laminin, beta-2 (laminin S) (LAMB2; p = 0.0078, OR = 2.26 95% CI 1.24-4.14), aldehyde dehydrogenase 1 family-member A1 (ALDH1A1; p = 0.016, OR = 1.05 95% CI 1.01-1.1), and histone cluster-1 H3e (HIST1H3E; p = 0.03, OR = 0.975 95% CI 0.953-0.998) differentiating between medicated PD subjects versus controls. Using these four biomarkers for PD diagnosis, we achieved sensitivity and specificity of more than 80%. These biomarkers might be specific for PD diagnosis, since in AD subjects no significant results were observed. In the second validation, three genes (PSMA2, LAMB2 and ALDH1A1) demonstrated high reproducibility. This result supports previous studies of gene expression profiling and may facilitate the development of biomarkers for early diagnosis of PD.

Authors+Show Affiliations

Clinical Neurochemistry, National Parkinson Foundation Centre of Excellence Research Laboratories, Neurochemistry Laboratory, Clinic and Policlinic for Psychiatry, Psychosomatic and Psychotherapy, University of Würzburg, Füchsleinstr 15, 97080 Würzburg, Germany. edna.gruenblatt@kjpdzh.chNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

21069393

Citation

Grünblatt, Edna, et al. "Pilot Study: Peripheral Biomarkers for Diagnosing Sporadic Parkinson's Disease." Journal of Neural Transmission (Vienna, Austria : 1996), vol. 117, no. 12, 2010, pp. 1387-93.
Grünblatt E, Zehetmayer S, Jacob CP, et al. Pilot study: peripheral biomarkers for diagnosing sporadic Parkinson's disease. J Neural Transm (Vienna). 2010;117(12):1387-93.
Grünblatt, E., Zehetmayer, S., Jacob, C. P., Müller, T., Jost, W. H., & Riederer, P. (2010). Pilot study: peripheral biomarkers for diagnosing sporadic Parkinson's disease. Journal of Neural Transmission (Vienna, Austria : 1996), 117(12), 1387-93. https://doi.org/10.1007/s00702-010-0509-1
Grünblatt E, et al. Pilot Study: Peripheral Biomarkers for Diagnosing Sporadic Parkinson's Disease. J Neural Transm (Vienna). 2010;117(12):1387-93. PubMed PMID: 21069393.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Pilot study: peripheral biomarkers for diagnosing sporadic Parkinson's disease. AU - Grünblatt,Edna, AU - Zehetmayer,Sonja, AU - Jacob,Christian P, AU - Müller,Thomas, AU - Jost,Wolfgang H, AU - Riederer,Peter, Y1 - 2010/11/11/ PY - 2010/07/22/received PY - 2010/10/05/accepted PY - 2010/11/12/entrez PY - 2010/11/12/pubmed PY - 2011/11/15/medline SP - 1387 EP - 93 JF - Journal of neural transmission (Vienna, Austria : 1996) JO - J Neural Transm (Vienna) VL - 117 IS - 12 N2 - The need for an early and differential diagnosis of Parkinson's disease (PD) is undoubtedly one of the main quests of the century. An early biomarker would enable therapy to begin sooner and would, hopefully, slow or better prevent progression of the disease. We performed transcript profiling via quantitative RT-PCR in RNA originating from peripheral blood samples. The groups were de novo (n = 11) and medicated PD (n = 94) subjects and healthy controls (n = 34), while for negative control Alzheimer's disease (AD; n = 14) subjects were recruited as an additional neurodegenerative disease. The results were retested on a second recruitment consisting 22 medicated PD subjects versus 33 controls and 12 AD. Twelve transcripts were chosen as candidate genes, according to previous postmortem brain profiling. Multiple analyses resulted in four significant genes: proteasome (prosome, macropain) subunit-alpha type-2 (PSMA2; p = 0.0002, OR = 1.15 95% CI 1.07-1.24), laminin, beta-2 (laminin S) (LAMB2; p = 0.0078, OR = 2.26 95% CI 1.24-4.14), aldehyde dehydrogenase 1 family-member A1 (ALDH1A1; p = 0.016, OR = 1.05 95% CI 1.01-1.1), and histone cluster-1 H3e (HIST1H3E; p = 0.03, OR = 0.975 95% CI 0.953-0.998) differentiating between medicated PD subjects versus controls. Using these four biomarkers for PD diagnosis, we achieved sensitivity and specificity of more than 80%. These biomarkers might be specific for PD diagnosis, since in AD subjects no significant results were observed. In the second validation, three genes (PSMA2, LAMB2 and ALDH1A1) demonstrated high reproducibility. This result supports previous studies of gene expression profiling and may facilitate the development of biomarkers for early diagnosis of PD. SN - 1435-1463 UR - https://www.unboundmedicine.com/medline/citation/21069393/Pilot_study:_peripheral_biomarkers_for_diagnosing_sporadic_Parkinson's_disease_ L2 - https://doi.org/10.1007/s00702-010-0509-1 DB - PRIME DP - Unbound Medicine ER -