A molecular signature in blood identifies early Parkinson’s disease

• DOI: 10.1186/1750-1326-7-26
• Publication Date: 2012-08-21T14:21:03Z
• Authors: Leonid Molochnikov; Jose M Rabey; Evgenya Dobronevsky; Ubaldo Bonuccelli; Roberto Ceravolo; Daniela Frosini; Edna Grünblatt; Peter Riederer; Christian Jacob; Judith Aharon-Peretz; Yulia Bashenko; Moussa BH Youdim; Silvia A Mandel
• Keywords: Gene signature

Abstract Background The search for biomarkers in Parkinson’s disease (PD) is crucial to identify the early and monitor effectiveness of neuroprotective therapies. We aim assess whether a gene signature could be detected blood from early/mild PD patients that support diagnosis PD, focusing on genes found particularly altered substantia nigra sporadic PD. Results transcriptional expression seven selected was examined samples 62 stage 64 healthy age-matched controls. Stepwise multivariate logistic regression analysis identified five as optimal predictors PD: p19 S-phase kinase-associated protein 1A (odds ratio [OR] 0.73; 95% confidence interval [CI] 0.60–0.90), huntingtin interacting protein-2 (OR 1.32; CI 1.08–1.61), aldehyde dehydrogenase family 1 subfamily A1 0.86; 0.75–0.99), 19 S proteasomal PSMC4 0.60–0.89) heat shock 70-kDa 8 1.39; 1.14–1.70). At 0.5 cut-off panel yielded sensitivity specificity detecting 90.3 89.1 respectively area under receiving operating curve (ROC AUC) 0.96. performance five-gene classifier de novo individuals alone composing cohort (n = 38), resulted similar ROC with an AUC 0.95, indicating stability model also, patient medication had no significant effect predictive probability (PP) risk. ability validated independent 30 at advanced classifying correctly all cases (100% sensitivity). Notably, nominal average value PP (0.95 (SD 0.09)) this higher than group (0.83 0.22)) , suggesting potential severity. Lastly, fully discriminated between Alzheimer’s 29). Conclusions findings provide evidence diagnose possible diagnostic detection asymptomatic before overt disorder.