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Biochim Biophys Acta. 2010 Aug;1801(8):839-45. doi: 10.1016/j.bbalip.2010.03.010. Epub 2010 Mar 27.

Cholesterol changes in Alzheimer's disease: methods of analysis and impact on the formation of enlarged endosomes.

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Centre de Recherche de l'Institut du Cerveau et de la Moelle, CNRS UMR7225, INSERM UMR975 and UPMC, Hôpital de la Pitié-Salpêtrière, 75013 Paris, France.


An increasing number of results implicating cholesterol metabolism in the pathophysiology of Alzheimer's disease (AD) suggest cholesterol as a target for treatment. Research in genetics, pathology, epidemiology, biochemistry, and cell biology, as well as in animal models, suggests that cholesterol, its transporter in the brain, apolipoprotein E, amyloid precursor protein, and amyloid-beta all interact in AD pathogenesis. Surprisingly, key questions remain unanswered due to the lack of sensitive and specific methods for assessing cholesterol levels in the brain at subcellular resolution. The aims of this review are not only to discuss the various methods for measuring cholesterol and its metabolites and to catalog results obtained from AD patients but also to discuss some new data linking high plasma membrane cholesterol with modifications of the endocytic compartments. These studies are particularly relevant to AD pathology, since enlarged endosomes are believed to be the first morphological change observed in AD brains, in both sporadic cases and Down syndrome.

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