Abstract
The understanding of cholesterol and its pathogenesis to Alzheimer’s disease (AD) pathogenic process is important for the possible prevention of AD. High fibre diets that contain phytosterols have been shown to lower LDL and increase HDL cholesterol and are implicated in membrane cholesterol and amyloid beta (Aβ) homeostasis. The convergence of diet and AD may be related to the effects of phytosterols since plasma cholesterol is closely linked and regulated by phytosterols. Dietary fibre modifications that are low in fat and glucose reduce the risk for AD by not only effecting cell membranes and nutrient sensing G coupled receptors but also by regulating number of nuclear receptors such as histone deacetylases (HDAC) and peroxisome proliferator activated receptors (PPAR) that control glucose, fatty acids and cholesterol and have significant effects on the brain cholesterol homeostasis and amyloidosis. The peripheral sink Aβ hypothesis indicates that the peripheral clearance of Aβ and its regulation by dietary phytosterols is of substantial interest since it may delay hypercholesterolemia and the early onset of amyloid plaque development. Liver disease has been of central importance with aging and programmed cell death pathways. Nutritional therapy has emerged as a novel approach to control appetite and the role of nutrigenomics as an early nutritional therapy may assist genes to delay liver and brain diseases such as Parkinson’s disease (PD) and Huntington’s disease (HD) that are associated with aging. The understanding of phytosterols and the role of these lipids in drug therapy such as cholesterol lowering drugs may provide molecular mechanisms that are involved in the regulation of cell Aβ clearance and metabolism. High fibre diets also contain various fatty acids such as the short chain fatty acids (SCFA) and the understanding of synergistic effects of SCFA and phytosterols in glucose regulation and cholesterol homeostasisis important to our understanding of diet, lifestyle and drugs in relation to peripheral amyloidosis and gene expression that play an early role in the development of AD.
Highlights
Environmental factors such as exercise, circadian rhythms abnormalities, oxidative stress and aspects of various diets in Western countries are of considerable importance when considering the risk for Alzheimer’s disease (AD)
Detailed studies have previously shown that plasma high density lipoprotein (HDL) and low density lipoprotein (LDL) cholesterol levels in AD patients when compared to age matched individuals [39,40,41] were significantly correlated to cognitive decline [41]
The cholesteryl esters have a profound effect on amyloid precursor protein (APP) processing and inhibition of the ACAT1 enzyme may reduce Aβ with effects on Aβ plaque development [54]. Both enzymes are closely involved in LDL receptor regulation and several reviews have shown that LDL receptors (LDLr) are involved in cholesterol homeostasis, APP processing and AD pathogenesis [55,56,57]
Summary
Environmental factors such as exercise, circadian rhythms abnormalities, oxidative stress and aspects of various diets in Western countries are of considerable importance when considering the risk for Alzheimer’s disease (AD). Molecular mechanisms that are involved in the regulation of cell Aβ clearance and metabolism require appropriate changes to diets such as high fibre diets that promote caloric restriction and allow consumption of diets that are low in fat and high in antioxidants, trace minerals and fish that are associated with appetite control and decreased risk for AD The aim of these dietary strategies will accelerate liver and brain cholesterol metabolism with improvements and reversal of non alcoholic fatty liver disease (NAFLD) and maintenance of peripheral Aβ metabolism (Figure 1 ref [2]). The role of fatty acids [28,29,30] and phytosterols on liver nutrient sensing genes such as Sirtuin 1 (Sirt 1) and G coupled protein receptors (GPCR) needs to be further addressed with relevance to the treatment of appetite dysregulation, NAFLD and the metabolic syndrome in obesity and diabetes that are chronic diseases associated with the increased risk for AD [31]
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