Evidence-Based Discriminant Analysis: A New Insight into Iron Profile for the Diagnosis of Parkinson's Disease.

INTRODUCTION: Parkinson's disease is the second most common neurodegenerative disorder. Neurochemical studies have implicated metals in pathogenesis of PD. OBJECTIVES: To examine the association of serum iron, transferrin, ferritin, transferrin saturation and UIBC in PD patients and to derive the Discrimination Function with scores of these variables to correctly classify PD cases and healthy controls. METHODS: In the present study, identification of biomarker pool in case-control study involving 79 PD cases and 80 healthy controls were performed. RESULTS: The results of independent t-test analysis showed that PD cases presented significantly higher (P < 0.01) level of transferrin, total iron binding capacity (TIBC), unsaturated iron binding capacity (UIBC) and urea than controls. As only one-third of transferrin is saturated with iron, so the transferrin present in serum has the extra binding capacity (67%), this is called UIBC. Discriminant analysis was performed to determine the factors that best discriminate between the categories of an outcome variables (Disease status = PD and Control) and total of five biochemical independent variables (UIBC, transferrin, iron, transferrin saturation, and copper) were taken into consideration. UIBC has emerged out to be highest discriminating, powerful and independent variable among considered independent variables, which indicates iron deficiency. After development of Discriminant Function (Z) and calculation of discriminant function cut points, a cross-validation analysis of PD cases and controls were conducted. The sensitivity of the developed model was 98.73% and specificity 83.75%. Receiver operating characteristics (ROC) was plotted, and the findings of ROC curve corroborated with the results obtained from discriminant function analysis. CONCLUSION: Prospective validation of Discriminant model in large cohort is warranted in future studies.

Role of Iron and Copper in the Pathogenesis of Parkinson's Disease.

Parkinson's disease (PD) is an old age disorder of basal ganglia which involves oligomerization of α-synuclein protein and formation of intercellular inclusions known as "Lewy bodies" in substantia nigra and caudate nuclei in brain which is progressive in nature. It is second most prevalent neurodegenerative disorder characterized by tremor at rest, muscle rigidity, slowness of movement (bradykinesia, akinesia), and changes in posture (instability). Both excess and deficiency in levels of transition metals (especially iron, copper) can be detrimental to the central nervous system. Abnormalities in iron (Fe) and copper (Cu) metabolism have been reported to produce oxidative stress which is one of the major cause in pathogenesis of PD. In the present study 35 PD patients and 33 controls of Northern Indian population were included and serum levels of Fe, Cu and ceruloplasmin (Cp) were measured. Serum Fe (p < 0.01) and Cu (p < 0.01) levels were found to be significantly decreased in PD, whereas there was no significant change in Cp levels in PD patients as compared to controls. These results suggest the existence of a defect in iron which over the time, may hasten the entry of iron into the brain and decrease iron in the extracellular compartment in PD patients.