PLoS One. 2012;7(8):e43595. Epub 2012 Aug 27.
Potashkin JA, Santiago JA, Ravina BM, Watts A, Leontovich AA.
Source
The
Cellular and Molecular Pharmacology Department, Rosalind Franklin
University of Medicine and Science, The Chicago Medical School, North
Chicago, Illinois, United States of America.
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.
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