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Biochim Biophys Acta. 2010 Aug;1801(8):966-74. doi: 10.1016/j.bbalip.2010.05.002. Epub 2010 May 7.

Role of amyloid beta in lipid homeostasis.

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  • 1Deutsches Institut für DemenzPrävention (DIDP), Neurodegeneration and Neurobiology, Saarland University, 66421 Homburg/Saar, Germany.

Abstract

Alzheimer's disease (AD), the most common neurodegenerative disorder, which affects more than 35 million people worldwide, is characterized by a massive accumulation of tangles and amyloid plaques. Several risk factors linked to lipid homeostasis have been identified. Apolipoprotein E (ApoE), which also has a strong impact in coronary artery disease, is besides aging the most prominent risk factor in sporadic AD. High levels of lipoproteins and cholesterol increase the risk of AD and some cholesterol lowering drugs like statins seem to correlate with a reduced risk for dementia. Moreover, cholesterol increases amyloid beta (Abeta) production, which is derived from amyloid precursor protein (APP) by proteolytic processing. Beside cholesterol, other lipids that strongly modulate APP processing could be identified and interestingly the APP cleavage products itself regulate lipid homeostasis resulting in complex regulatory feedback cycles. Here, we review the mechanistic link of cholesterol and sphingolipid homeostasis and APP processing and the consequence of this bidirectional link for and in AD. Although cholesterol is the best studied brain lipid in AD, many other lipids are involved in the Abeta-lipid regulatory system and some of these lipids exceed the cholesterol effect on Abeta production [1-5]. This involvement is bidirectional. On the one hand, lipids control APP processing and, on the other hand, APP processing controls the levels of several key lipids [6, 7]. Beside the physiological function of APP processing in lipid homeostasis, under pathological conditions like AD, these regulating (feedback-) cycles are dysfunctional. Additionally, mutual influence of lipids and APP processing raises the question if altered lipid homeostasis is the cause or consequence of AD.

Copyright 2010 Elsevier B.V. All rights reserved.

PMID:
20452461
[PubMed - indexed for MEDLINE]
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