Plasma-membrane composition plays a crucial role in most of the cellular functions that depend on membrane processes. In virtually all cell types the proteolytic processing of Alzheimer amyloid precursor protein (APP) to generate soluble APP (sAPP) is believed to occur at the plasma membrane or in its immediate proximity. Alteration of this metabolic pathway has been linked to the pathogenesis of Alzheimer's disease. We analysed the effect of membrane cholesterol enrichment on APP metabolism. Incubation of COS cells with increasing concentrations of nonesterified cholesterol carried by rabbit β-very low-density lipoprotein caused a dose-dependent inhibition of sAPP release : 70 % inhibition with 10 µg\ml non-esterified cholesterol. A less pronounced inhibitory effect was observed on treatment with
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