Identification of mitophagy-associated proteins (MAPs) profile as potential plasma biomarkers of idiopathic Parkinson’s disease

Abstract

Abstract It is noteworthy that despite many efforts to screen biochemical plasma markers for PD diagnosis, there is still not an accepted and validated surrogate biomarker. To decipher the role of the mitophagy-associated proteins (MAPs) in idiopathic PD subjects and investigate whether the diagnosis is related to MAP levels and whether the levels predict motor and cognitive progression. This prospective study totally enrolled 150 PD patients. 71 age-matched controls (CN) alongside 41 PDs in two cohorts: modeling cohort (cohort 1), including 121 PD, 52 CN, and 29 PDs; validated cohort (cohort 2), including 29 PD, 19 CN, and 12 PDs. The MAPs (PINK1, Parkin, PGAM5, BNIP3, and p-TBK1) and a-synuclein-related proteins (ASPs: total a-synuclein, phosphorylated a-synuclein, and a-synuclein oligomer) levels were measured using an electrochemiluminescence immunoassay. MAPs are elevated in the plasma of PD patients. The PINK1, Parkin, and PGAM5 displayed the top three measurable increase trends in amplitude compared to BNIP3 and p-TBK1. Moreover, the AUCs of PINK1, PGAM5, and Parkin were ranked the top three MAP candidates in diagnosis accuracy for PD from CN, but the MAPs hard to differentiate the PD from PDs. In addition, Plasma PINK1 positively correlated with total UPDRS, UPDRS part III, and H-Y stage, with no significant correlations with HAMA, HAMD, and RBD scores. As expected, higher plasma PINK1-Parkin levels and prominent diagnostic accuracy in A-synuclein (+) subjects than in A-synuclein (-) subjects. These results uncover that plasma MAPs (PINK1, Parkin, and PGAM5) may be potentially useful target biomarkers for PD diagnosis. Studies on larger cohorts would be required to test whether elevated plasma MAP levels are related to PD risk or prediction.