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FEBS Lett. 2006 Oct 9;580(23):5525-32. Epub 2006 Jun 23.

Amyloid excess in Alzheimer's disease: what is cholesterol to be blamed for?

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Department of Molecular and Developmental Genetics, Flanders Interuniversity Institute of Biotechnology, VIB11, and Catholic University of Leuven, Campus Gasthuisberg, Heerstraat 49, 3000 Leuven, Belgium.


A link between alterations in cholesterol homeostasis and Alzheimer's disease (AD) is nowadays widely accepted. However, the molecular mechanism/s underlying such link remain unclear. Numerous experimental evidences support the view that changes in neuronal membrane cholesterol levels and/or subcellular distribution determine the aberrant accumulation of the amyloid peptide in the disease. Still, this view comes from rather contradictory data supporting the existence of either high or low brain cholesterol content. This is of particular concern considering that therapeutical strategies aimed to reduce cholesterol levels are already being tested in humans. Here, we review the molecular mechanisms proposed and discuss the perspectives they open.

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