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
