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pubmed-article:20477946pubmed:abstractTextEpidemiological studies have shown an association between statin use and a decreased risk of dementia. However, the mechanism by which this beneficial effect is brought about is unclear. In the context of Alzheimer's disease, at least three possibilities have been studied; reduction in amyloid beta peptide (Abeta) production, the promotion of alpha-secretase cleavage and positive effects on neurite outgrowth. By investigating the effects of mevalonate pathway blockade on neurite outgrowth using real-time imaging, we found that rather than promote the production of neurite extensions, inhibition rapidly induced cell rounding. Crucially, neurite-like structures were generated through the persistence of cell-cell and cell-substrate adhesions and not through a mechanism of positive outgrowth. This effect can be strikingly enhanced by the over-expression of human amyloid precursor protein and is isoprenoid rather than cholesterol dependent.lld:pubmed
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pubmed-article:20477946pubmed:articleTitleNeurite-like structures induced by mevalonate pathway blockade are due to the stability of cell adhesion foci and are enhanced by the presence of APP.lld:pubmed
pubmed-article:20477946pubmed:affiliationPharmaceutical Sciences Division, King's College London, London, UK.lld:pubmed
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