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Abstract Metalloproteins utilizes cellular metals which plays a crucial function in brain that linked with neurodegenerative disorders. Parkinson’s disease (PD) is a neurodegenerative disorder that affects geriatric population world-wide. Twenty-four metal-binding protein networks were investigated to identify key regulating protein hubs in PD blood and brain. Amongst, aluminum, calcium, copper, iron, and magnesium protein hubs are the key regulators showing the ability to classify PD from control based on thirty-four classification algorithms. Analysis of these five metal proteins hubs showed involvement in environmental information processing, immune, neuronal, endocrine, aging, and signal transduction pathways. Furthermore, gene expression of functional protein in each hub showed significant upregulation of EFEMP2, MMP9, B2M, MEAF2A, and TARDBP in PD. Dysregulating hub proteins imprint the metal availability in a biological system. Hence, metal concentration in serum and cerebrospinal fluid were tested, which were altered and showed significant contribution towards gene expression of metal hub proteins along with the previously reported PD markers. In conclusion, analyzing the levels of serum metals along with the gene expression in PD opens up an ideal and feasible diagnostic intervention for PD. Hence, this will be a cost effective and rapid method for the detection of Parkinson’s disease.