Serum metabolic profiling for detection of Alzheimer's disease / Che Nor Adlia Enche Ady

• Main Author: Enche Ady, Che Nor Adlia
• Format: Thesis
• Language: English
• Published: 2017
• Subjects: Diseases of the circulatory (Cardiovascular) system; Diseases of the musculoskeletal system
• Online Access: https://ir.uitm.edu.my/id/eprint/38869/1/38869.pdf; https://ir.uitm.edu.my/id/eprint/38869/

Alzheimer's disease (AD) is characterized by loss of memory and deterioration of cognitive function. To date, AD treatment remains a great challenge as pathogenesis of this disease is still poorly understood. Reliable AD biomarkers would therefore be of high relevance, not only to assist early detection but also to uncover potential drug targets that can be manipulated to slow down disease progression. This study compared metabolomic profiles of blood serum from AD patients to those of the non-demented controls. Qualitative metabolomic profiles of blood serum were acquired using the liquid chromatography/mass spectrometry quadrupole time-of-flight (LC-MSQTOF) and Nuclear Magnetic Resonance (NMR). The most important finding that emerged from this study is that lipids and amino acids are responsible for the metabolic changes linked to AD. The present study has revealed four LC-MS-derived metabolites [(N-(2- hydroxyethyl)palmita ide, N-(2-hydroxyethyl)icosanamide, dihydroceramide, Phyto sphingosine] and four NMR-derived metabolites (isoleucine, creatinine, VLDL, lipid) that might be implicated in AD pathogenesis. These metabolites panel may serve as potential biomarkers which are associated with neuronal P amyloid release, apoptosis, dysregulated energy metabolism and brain oxidative impairment that will lead to neuronal cell death. In terms of pathways, sphingolipid metabolism and biosynthesis of valine, leucine and isoleucine were found to be perturbed in AD. Comparison of metabolomic profiles obtained through LC-MS and NMR indicated high complementarity between these two platforms. The present findings demonstrated the complementary nature of NMR and LC/MS, implying that combination use of NMR and LC/MS facilitated a more comprehensive profiling of metabolite.