Biosignatures for Parkinson’s Disease and Atypical Parkinsonian Disorders PatientsReportar como inadecuado

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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.

Autor: Judith A. Potashkin , Jose A. Santiago, Bernard M. Ravina, Arthur Watts, Alexey A. Leontovich



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