700 Journals and 15,000,000 Readers Each Journal is getting 25,000+ ReadersThis Readership is 10 times more when compared to other Subscription Journals (Source: Google Analytics)
Hypercholesterolemia is known as a major risk of atherosclerosis. However, recent studies revealed that elevated level of LDL (“known as bad cholesterol”) predisposes also to dementia, stroke and neuropathies including Alz-heimer’s disease (AD). The relationship between the blood cholesterol level and AD has not been completely ex-plained, however, the clusterin/ApoJ role seems to be pivotal. Clusterin is a glycoprotein expressed by various cell types. Moreover, Clu/ApoJ is secreted into body fluids and its expression is stimulated in response to raised sterol levels. In blood, Clu/ApoJ interacts with other lipoproteins, plasma proteins or lipids, including cholesterol, and is also capable to translocate through the blood-brain barrier. Additionally, the high blood plasma levels of choles-terol promote formation of plasma membrane lipid rafts, enriched in β-secretase enzyme. Consequently, the ab-normal amyloid β precursor protein (AβPP) cleavage may occur and neurotoxic amyloid β is produced. Thus, the intensity of amyloid β processing is apparently related to cholesterol concentration, and could be limited by cho-lesterol-depleting agents such as statins. Interestingly, Clu/ApoJ is not merely transported from blood plasma into brain, but at the same time it is secreted by astrocytes to extracellular fluid. Clu/ApoJ interacts with Aβ1-40 and is accumulated in peptide plaques. To maintain Aβ in soluble form, the extracellular Clu/ApoJ is simultaneously complexed with Aβ. Finally, intracellular variant of clusterin is admitted to mediate the activation of Ca2+-permeable ion channels, which initiate Aβ-induced neuronal cell apoptosis. Taken together, we hypothesize, that Clu/ApoJ plays an important role in cholesterol-dependent AD pathogenesis and should be seriously considered as a component in AD pathology.
To read the full article Peer-reviewed Article PDF
Author(s): Beata Pajak Arkadiusz Orzechowski Barbara Gajkowska
Hypercholesterolemia, atherosclerosis, cholesterol, neuropathies, Alzheimerâs disease, glycoprotein