Metallomic Biomarkers in Cerebrospinal fluid and Serum in patients with Parkinson’s disease in Indian population

Abstract

Parkinson's disease (PD) is a neurodegenerative disease with the absence of markers for diagnosis. Several studies on PD reported the elements imbalance in biofluids as biomarkers. However, their results remained inconclusive. This study integrates metallomics, multivariate and artificial neural network (ANN) to understand element variations in CSF and serum of PD patients from the largest cohort of Indian population to solve the inconsistent results of previous studies. Also, this study is aimed to (1) ascertain a common element signature between CSF and serum. (2) Assess cross sectional element variation with clinical symptoms. (3) Develop ANN models for rapid diagnosis. A metallomic profile of 110 CSF and 530 serum samples showed significant variations in 10 elements of CSF and six in serum of patients compared to controls. Consistent variations in elements pattern were noticed for Calcium, Magnesium and Iron in both the fluids of PD, which provides feasible diagnosis from serum. Furthermore, implementing multivariate analyses showed clear classification between normal and PD in both the fluids. Also, ANN provides 99% accuracy in detection of disease from CSF and serum. Overall, our analyses demonstrate that elements profile in biofluids of PD will be useful in development of diagnostic markers for PD.

Promising Metabolite Profiles in the Plasma and CSF of Early Clinical Parkinson's Disease

“…By analyzing blood plasma and CSF using HRMS metabolomics (Hatano et al, 2016 ; Sanyal et al, 2016 ), our study set out to discover metabolic profiles that allow the differentiation of PD from control state and to gain insight into the molecular pathogenesis of the disease. Blood plasma and CSF were used to investigate whether findings can be translated from one matrix to the other (CSF to plasma) and therefore increasing the possibility of moving to a prodromal investigation of PD.…”

Elevated circulating magnesium levels in patients with Parkinson’s disease: a meta-analysis

“… 24 – 27 Also, a few studies probably tended no statistical difference in Mg levels between PD patients and healthy populations. 28 , 29 …”

Targeting the Microglial NLRP3 Inflammasome and Its Role in Parkinson's Disease

“…Parkinson's disease (PD) is characterized by progressive loss of dopaminergic neurons in the substantia nigra (SN) and accumulation of Lewy bodies in the brain with subsequent motor dysfunction . Extensive clinical and experimental research suggests that the association of microglial activation and neuroinflammation may be key regulators of dopaminergic neuronal loss in PD .…”

“…Parkinson's disease (PD) is characterized by progressive loss of dopaminergic neurons in the substantia nigra (SN) and accumulation of Lewy bodies in the brain with subsequent motor dysfunction. 1,2 Extensive clinical and experimental research suggests that the association of microglial activation and neuroinflammation may be key regulators of dopaminergic neuronal loss in PD. 3,4 However, chronic activation of microglia and excessive release of these proinflammatory mediators in the brain can result in expression of costimulatory molecules, which results in neuroinflammation and neuronal dysfunction.…”