biosignatures for parkinson’s disease and atypical parkinsonian disorders patients生物特征对帕金森病和非典型帕金森疾病的病人.pdfVIP

Biosignatures for Parkinson’s Disease and Atypical Parkinsonian Disorders Patients 1 1 2,3 4 5 Judith A. Potashkin *, Jose A. Santiago , Bernard M. Ravina , Arthur Watts , Alexey A. Leontovich 1The Cellular and Molecular Pharmacology Department, Rosalind Franklin University of Medicine and Science, The Chicago Medical School, North Chicago, Illinois, United States of America, 2 Neurology Department, University of Rochester School of Medicine, Rochester, New York, United States of America, 3 Biogen Idec, Cambridge, Massachusetts, United States of America, 4 Department of Biostatistics, University of Rochester School of Medicine, Rochester, New York, United States of America, 5 Division of Biomedical Statistics and Informatics, Mayo Clinic, Rochester, Minnesota, 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 diagnos