title: Biosignatures for Parkinson's disease and atypical parkinsonian disorders patients.
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.affiliation: 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.edu
authors.forename: Judith A
authors.initials: JA
authors.lastname: Potashkin
authors.forename: Jose A
authors.initials: JA
authors.lastname: Santiago
authors.forename: Bernard M
authors.initials: BM
authors.lastname: Ravina
authors.forename: Arthur
authors.initials: A
authors.lastname: Watts
authors.forename: Alexey A
authors.initials: AA
authors.lastname: Leontovich
mesh_terms: D000368:Aged; D015415:Biomarkers / Q000097:blood / Q000378:metabolism; D016022:Case-Control Studies; D005260:Female; D051557:Hepatocyte Nuclear Factor 4 / Q000378:metabolism; D006801:Humans; D007328:Insulin / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D020411:Oligonucleotide Array Sequence Analysis; D010300:Parkinson Disease / Q000097:blood / Q000175:diagnosis* / Q000235:genetics / Q000378:metabolism*; D025341:Principal Component Analysis; D020033:Protein Isoforms / Q000097:blood / Q000235:genetics; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D015203:Reproducibility of Results; D012680:Sensitivity and Specificity; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
chemical_list: D015415:Biomarkers; C496592:HNF4A protein, human; D051557:Hepatocyte Nuclear Factor 4; D007328:Insulin; D020033:Protein Isoforms; D012333:RNA, Messenger; D014409:Tumor Necrosis Factor-alpha