Alzheimer's disease: cholesterol a menace?
ABSTRACT Alzheimer's disease (AD) is the most prevalent neurodegenerative disease manifested by cognitive and memory deterioration, culminating in a spectrum of neuropsychiatric disturbances and the impairment of daily activities. AD is a multifactorial disease with a range of contributing factors which includes genes and diet. The magnitude of AD is reflected in the loss of individuality of the affected person and in the terminal course through which the disease develops. In this review, we aim to provide a background on AD and the contribution of cholesterol in the etiology of Alzheimer's. Cholesterol seems to be intimately linked with the generation of amyloid plaques, which is central to the pathogenesis of AD. Although there are conflicting reports on the role of cholesterol in AD, majority of the studies point out the positive association of cholesterol with AD.
- SourceAvailable from: Natalia N Nalivaeva[show abstract] [hide abstract]
ABSTRACT: Lipid rafts are membrane domains, more ordered than the bulk membrane and enriched in cholesterol and sphingolipids. They represent a platform for protein-lipid and protein-protein interactions and for cellular signaling events. In addition to their normal functions, including membrane trafficking, ligand binding (including viruses), axonal development and maintenance of synaptic integrity, rafts have also been implicated in the pathogenesis of several neurodegenerative diseases including Alzheimer's disease (AD). Lipid rafts promote interaction of the amyloid precursor protein (APP) with the secretase (BACE-1) responsible for generation of the amyloid β peptide, Aβ. Rafts also regulate cholinergic signaling as well as acetylcholinesterase and Aβ interaction. In addition, such major lipid raft components as cholesterol and GM1 ganglioside have been directly implicated in pathogenesis of the disease. Perturbation of lipid raft integrity can also affect various signaling pathways leading to cellular death and AD. In this review, we discuss modulation of APP cleavage by lipid rafts and their components, while also looking at more recent findings on the role of lipid rafts in signaling events.Frontiers in Physiology 01/2012; 3:189.
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ABSTRACT: Desmosterol is a C27 sterol intermediate in cholesterol synthesis generated during the metabolic pathway that transforms lanosterol into cholesterol. It has become of particular interest in the pathogenesis of Alzheimer's disease (AD) because of the report that the activity of the gene coding for the enzyme DHCR24, which metabolizes desmosterol to cholesterol, is selectively reduced in the affected areas of the brain. Any change in the pattern of C27 sterol intermediates in cholesterol synthesis merits investigation with respect to the pathogenesis of AD, since neurosteroids such as progesterone can modulate the tissue levels. We therefore analyzed the C27 sterol composition using a metabolomics approach that preserves the proportion of the different sterol intermediates. In AD, the proportion of desmosterol was found to be less than that of age-matched controls. The findings do not directly support the focus on Seladin-1, although they could reflect different stages of a slowly progressive disease.Journal of Alzheimer's disease: JAD 10/2012; · 4.17 Impact Factor