Abstract
A connection between lipid rafts and Alzheimer's disease has been studied during the last decades. Mathematical modeling approaches have recently been used to correlate the effects of lipid composition changes in the physicochemical properties of raft-like membranes. Here we propose an agent based model to assess the effect of lipid changes in lipid rafts on the evolution and progression of Alzheimer's disease using lipid profile data obtained in an established model of familial Alzheimer's disease. We have observed that lipid raft size and lipid mobility in non-raft domains are two main factors that increase during age and are accelerated in the transgenic Alzheimer's disease mouse model. The consequences of these changes are discussed in the context of neurotoxic amyloid β production. Our agent based model predicts that increasing sterols (mainly cholesterol) and long-chain polyunsaturated fatty acids (LCPUFA) (mainly DHA, docosahexaenoic acid) proportions in the membrane composition might delay the onset and progression of the disease.
Highlights
Alzheimer’s disease (AD) is the most frequent dementia worldwide, affecting more than 40 million people worldwide, with a prevalence of around 10% of the population above 65 years, which doubles every 10 years (Han and Han, 2014)
The model showed that the composition of monoenoic fatty acids, docosahexaenoic acid (DHA), and n-6 long-chain polyunsaturated fatty acids (LCPUFA) on rafts domains and total membrane followed the changes demonstrated experimentally in both Wild-type and amyloid precursor protein (APP)/PS1 mice (Fabelo et al, 2012)
We propose that the increased proportion of lipid rafts is one of the consequences of aging, and that this trend is accelerated in AD patients, which can positively feedback the production of β-amyloid
Summary
Alzheimer’s disease (AD) is the most frequent dementia worldwide, affecting more than 40 million people worldwide, with a prevalence of around 10% of the population above 65 years, which doubles every 10 years (Han and Han, 2014). AD is a degenerating irreversible disease that impairs memory and cognitive abilities and, at present, has no cure. AD occurs in two forms: the familial and the sporadic. The familial type is known to be associated to several well-defined genetic alterations (Tanzi, 2012; Loy et al, 2014), it does only explain
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