Role of Nutraceuticals in Ameliorating Effects of High Fat Diet in Alzheimer's Disease

Abstract

Alzheimer’s disease (AD) is the most common form of dementia that affects almost 50 million people worldwide. The pathology results in progressive loss of neurons resulting in worsening memory and cognitive impairment. Obesity is emerging as the top modifiable risk factor for AD. Despite the recent approval of new therapies these currently show limited effectiveness. In this context the bioactivity of anti-inflammatory nutraceuticals derived from plants may offer viable alternatives with the potential to modulate or slow disease progress if used in a prophylactic manner. Accordingly, the aim of the work presented in this thesis is to clarify the ability of green tea catechin (GTC) and hydroxytyrosol (HT) either alone or in combination to affect microglial function related to neuro-inflammation. To this end, both in vitro and in vivo approaches were used to test the hypothesis that plant polyphenols can dampen mechanisms leading to neuroinflammation and ultimately neuronal death. In vitro: the mouse microglial cell line, BV2, was stimulated with agents relevant to AD (amyloid peptide and ox-LDL) in the presence or absence of the nutraceuticals. Analysing a range of cellular functions related to inflammation the data shows that both these molecules were able to inhibit or block the inflammatory effects produced by amyloid peptide and ox LDL. In vivo study: the 3xTg-AD and APPKI-AD mouse models were administered a high fat diet to model obesity and produce a pro-inflammatory scenario. The data herein provides evidence that GTC and/or HT were generally able to reduce the pro-disease effects of high fat feeding in both the mouse model strains. While the data presented requires further experimentation to reveal mechanistic details, taken together, the present studies demonstrated that GTC and HT treatment solely or in combination possesses anti-neuroinflammatory activity and might serve as potential therapeutic agents for treating neuroinflammatory diseases.