Cholesterol and Alzheimer's disease: statins, cholesterol depletion in APP processing and Abeta generation.
Molecular and more specifically subcellular analyses of the neurodegenerative mechanisms involved in Alzheimer's disease (AD) had been considered most of the time an interplay of proteins and genes. However, some of the observations could not be explained this way. Recently, a number of research groups found the missing link ... lipids! Among the variety of lipids that had been investigated, most investigations had been focused on cholesterol and some derivatives. A recent statistic found that for every primary research article on AD and cholesterol/statins, approximately two reviews were published. This clearly reflects as much the interest in this topic, as it gives evidence that this field is still in its juvenile phase and most aspects have yet to be covered or clarified. To date there is evidently no final answer to whether this approach will eventually provide a therapeutic solution to treat or prevent AD. At the end of the day such answers can only be obtained from clinical studies and to date only two studies with a suitable design have published their results, one of them with preliminary results only. This review focuses on what we know about the cellular mechanisms involved in the AD-lipid connection and what kinds of problematic issues; theoretical and practical, are at hand.
Hartman
Tobias
T
Center for Molecular Biology Heidelberg (ZMBH), university of Heidelberg, Im Neuenheimer Feld 282, D-69120 Heidelberg, Germany.
D000544:Alzheimer Disease / Q000378:metabolism* / Q000517:prevention & control; D016229:Amyloid beta-Peptides / Q000378:metabolism*; D016564:Amyloid beta-Protein Precursor / Q000378:metabolism*; D000818:Animals; D000924:Anticholesteremic Agents / Q000627:therapeutic use; D002784:Cholesterol / Q000378:metabolism*; D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000627:therapeutic use*
D016229:Amyloid beta-Peptides; D016564:Amyloid beta-Protein Precursor; D000924:Anticholesteremic Agents; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D002784:Cholesterol