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Biosignatures for Parkinson's disease and atypical parkinsonian disorders patients.
PLoS One. 2012; 7(8):e43595.Plos

Abstract

Diagnosis of Parkinson' disease (PD) carries a high misdiagnosis rate due to failure to recognize atypical parkinsonian disorders (APD). Usually by the time of diagnosis greater than 60% of the neurons in the substantia nigra are dead. Therefore, early detection would be beneficial so that therapeutic intervention may be initiated early in the disease process. We used splice variant-specific microarrays to identify mRNAs whose expression is altered in peripheral blood of early-stage PD patients compared to healthy and neurodegenerative disease controls. Quantitative polymerase chain reaction assays were used to validate splice variant transcripts in independent sample sets. Here we report a PD signature used to classify blinded samples with 90% sensitivity and 94% specificity and an APD signature that resulted in a diagnosis with 95% sensitivity and 94% specificity. This study provides the first discriminant functions with coherent diagnostic signatures for PD and APD. Analysis of the PD biomarkers identified a regulatory network with nodes centered on the transcription factors HNF4A and TNF, which have been implicated in insulin regulation.

Authors+Show Affiliations

The Cellular and Molecular Pharmacology Department, Rosalind Franklin University of Medicine and Science, The Chicago Medical School, North Chicago, Illinois, United States of America. judy.potashkin@rosalindfranklin.eduNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

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

Language

eng

PubMed ID

22952715

Citation

Potashkin, Judith A., et al. "Biosignatures for Parkinson's Disease and Atypical Parkinsonian Disorders Patients." PloS One, vol. 7, no. 8, 2012, pp. e43595.
Potashkin JA, Santiago JA, Ravina BM, et al. Biosignatures for Parkinson's disease and atypical parkinsonian disorders patients. PLoS One. 2012;7(8):e43595.
Potashkin, J. A., Santiago, J. A., Ravina, B. M., Watts, A., & Leontovich, A. A. (2012). Biosignatures for Parkinson's disease and atypical parkinsonian disorders patients. PloS One, 7(8), e43595. https://doi.org/10.1371/journal.pone.0043595
Potashkin JA, et al. Biosignatures for Parkinson's Disease and Atypical Parkinsonian Disorders Patients. PLoS One. 2012;7(8):e43595. PubMed PMID: 22952715.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Biosignatures for Parkinson's disease and atypical parkinsonian disorders patients. AU - Potashkin,Judith A, AU - Santiago,Jose A, AU - Ravina,Bernard M, AU - Watts,Arthur, AU - Leontovich,Alexey A, Y1 - 2012/08/27/ PY - 2012/05/04/received PY - 2012/07/26/accepted PY - 2012/9/7/entrez PY - 2012/9/7/pubmed PY - 2013/2/21/medline SP - e43595 EP - e43595 JF - PloS one JO - PLoS One VL - 7 IS - 8 N2 - Diagnosis of Parkinson' disease (PD) carries a high misdiagnosis rate due to failure to recognize atypical parkinsonian disorders (APD). Usually by the time of diagnosis greater than 60% of the neurons in the substantia nigra are dead. Therefore, early detection would be beneficial so that therapeutic intervention may be initiated early in the disease process. We used splice variant-specific microarrays to identify mRNAs whose expression is altered in peripheral blood of early-stage PD patients compared to healthy and neurodegenerative disease controls. Quantitative polymerase chain reaction assays were used to validate splice variant transcripts in independent sample sets. Here we report a PD signature used to classify blinded samples with 90% sensitivity and 94% specificity and an APD signature that resulted in a diagnosis with 95% sensitivity and 94% specificity. This study provides the first discriminant functions with coherent diagnostic signatures for PD and APD. Analysis of the PD biomarkers identified a regulatory network with nodes centered on the transcription factors HNF4A and TNF, which have been implicated in insulin regulation. SN - 1932-6203 UR - https://www.unboundmedicine.com/medline/citation/22952715/Biosignatures_for_Parkinson's_disease_and_atypical_parkinsonian_disorders_patients_ L2 - https://dx.plos.org/10.1371/journal.pone.0043595 DB - PRIME DP - Unbound Medicine ER -