IRS1 and Parkinson disease: Although the levels of p-IRS-1S312 certainly overlapped between controls and PD patients, to the best of our knowledge, the present study is the first to provide biomarker-based evidence for the association between the altered neuronal p-IRS-1 with PD by means of the analysis of blood NDEVs, and this observation also hinted the role of dysfunctional insulin signaling pathway in the pathogenesis of PD.