Identification of Disease Biomarkers through Proteome Profiling of Mild Cognitive Impaired Patients

Abstract

Mild cognitive impairment (MCI) is a first-stage disease leading to Dementia and Alzheimer's Disease(AD). The prevalence of MCI varies from 3%-20% worldwide. The present study investigated the potential molecular alterations in MCI patients at the proteome and metabolome levels. Differentially expressed proteins were profiled using the patient's serum through two dimensional gel electrophoresis (2DE), while a metabolite profile was generated through GCMS analysis. Approximately >200 compounds were identified in total, comprising numerous novel metabolites. Out of these 200, 48 compounds were found to be significantly expressed in MCI compared to control subjects. The potential role of these disease-associated metabolites was assessed through a literature search. The insilico analysis performed to investigate the enrichment of the identified metabolites showed their involvement in several metabolic pathways altered in MCI. Moreover, mRNA expression analysis of SLIT-guidance ligand-1 (SLIT1), an axon guidance molecule involved in adult neurogenesis and growth differentiation factor 1 (GDF-1), which is implicated in early neuron development, were analyzed using Real-Time PCR which indicated that the SLIT-1 and GDF-1 expression was down-regulated in MCI patients. The possible role of endoplasmic reticulum (ER) stress in MCI was also evaluated by assessing the protein expression of a potent ER stress biomarker, activating transcription factor 6 (ATF6) through western blot. It was found to be upregulated in MCI. In conclusion, the present preliminary data highlights several aspects associated with MCI pathology, explicitly suggesting the significant role of differentially expressed proteins and metabolites which can serve as potential biomarkers for the early diagnosis, prognosis, and treatment of MCI