Parkinson’s disease (PD) as a progressive health issue effects on the central nervous system. It is well established that soluble -synuclein ( syn) oligomers cause neuronal death in the earliest stages of PD. So, development of sensitive and selective method for a-syn analysis is a challenge. Here an electrochemiluminescence (ECL) aptasensor designed for selective and ultrasensitive detection of α-syn oligomer using graphdiyne@polyaniline with N-doped active sites (GDY@PANI) as novel coreactant agent combined with CdTe@ZnS QD as luminescent lable for amplified self-enhanced electrochemiluminescence (ECL) response. For the first time a novel ECL sensing platform based on GDY@PANI/ CdTe@ZnS QD composite was designed using new co-reactant based on GDY. Compared to CdTe@ZnS QD, GDY/CdTe@ZnS QD, CdTe@ZnS QD/tri-propylamine and PANI/CdTe@ZnS QD, the GDY@PANI/CdTe@ZnS QD composite exhibited amplified ECL emissions and ECL efficiency of the proposed system also increased compared to more QDs based ECL systems. Under the optimal conditions, the proposed ECL aptasensor exhibited a wide linear range of 0.2 fM to 8 nM for α-syn oligomer determination with a low detection limit of 0.02 fM (S/N=3). The fabricated sensor has advantages of good reproducibility, high sensitivity and stability and being capable of detecting α-syn oligomer in human blood serum and also lysate of dopaminergic nerve cells. The obtained results confirmed that the GDY@PANI can be used as a novel co-reactant in development of the ECL based bio devices with great potential applicability for biomarkers analysis, diagnosis and management of Parkinson or other diseases.