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Access Type

WSU Access

Date of Award

January 2017

Degree Type

Dissertation

Degree Name

Ph.D.

Department

Nutrition and Food Science

First Advisor

Smiti Gupta

Abstract

Alzheimer’s disease (AD) is the most common cause of dementia in the aging population. It is characterized by cognitive decline and deposition of ß-amyloid plaques in the hippocampus. It has been shown that hypercholesterolemia induced by high cholesterol diet is associated with AD development. Increased level of oxidative stress has also been observed in AD patients. An important strategy to treat or delay the impairment is based on dietary modification, using food supplements. OPP, a water soluble fraction from oil palm fruit, rich in phenolics has been found to possess significant antioxidant activities. Its beneficial effects on cardiovascular diseases, diabetes and cancers have been previously reported. The current study was undertaken to investigate the effect of OPP in a rodent model for AD. Curcumin, a polyphenol extracted from the plant Curcuma longa, has shown its therapeutic benefits in Alzheimer’s disease and was used as a positive control. Our results showed the dietary cholesterol induced hypercholesterolemia which increased AD-like pathological changes in aged rats including β-amyloid accumulation & cognitive decline. OPP & curcumin attenuate the process of AD for their antioxidant and anti-inflammatory effects by improving these pathological changes. Furthermore, OPP down-regulated amyloidogenic genes APP and ß secretase (BACE1) expression as well as ApoE gene expression when the brain is in the presence of oxidative stress. In addition, metabolomic approach was also used to investigate the effect of OPP on metabolism changes due to the high cholesterol diet. Proton nuclear magnetic resonance (1H NMR) spectra was used to acquire the spectrum of samples. Multivariate analysis software, SIMCA-P+, was applied to demonstrate the differences in urinary 1H NMR profiles among the groups. Principal Component Analysis (PCA) score plots showed clear separation among all four groups indicating differences in their metabolomics profiles at the end point. OPLS regression analysis gave significant correlations between the urinary metabolomic profiles and escape latency using water maze (R2=0.7956) and the β amyloid burden (R2=0.7406). The metabolites responsible for the differences in the metabolomic profile among groups were then quantified using CHENOMX NMR metabolite database. Some metabolites from the tryptophan metabolism pathway were significantly altered in the cholesterol fed group (H) as compared to the treatment groups (HP, HC). Treatment with curcumin (HC) or OPP (HP) modulated the concentration of these metabolites closer to the control levels. This pathway has been shown to be perturbed in neurodegenerative diseases. Taken together, OPP exhibited a potential therapeutic effect in high cholesterol diet induced AD. Moreover, specific urinary metabolites may serve as non-invasive biomarkers for progression of neurodegenerative diseases including AD.

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