A growing body of evidence Implicates low membrane cholesterol in the pathogenesis of Alzheimer's disease (AD). Here we show that A beta 42 soluble oligomers accumulate more slowly and in reduced amount at the plasma membranes of PS-1L392V and APPV7171 fibroblasts from familial AD (FAD) patients enriched in cholesterol content than at the counterpart membranes. The A beta 42-induced production of reactive oxygen species (ROS) and the increase in membrane lipoperoxidation were also prevented by high membrane cholesterol, thus resulting in a higher resistance to amyloid toxicity with respect to control fibroblasts. On the other hand, the recruitment of amyloid assemblies to the plasma membrane of cholesterol-depleted fibroblasts was significantly increased, thus triggering an earlier and sharper production of ROS and a higher membrane oxidative injury. These results identify membrane cholesterol as being key to A beta 42 oligomer accumulation at the cell surfaces and to the following A beta 42-induced cell death in AD neurons. (C) 2009 Elsevier Inc. All rights reserved.
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St Petersburg Inst Bioregulat & Gerontol, St Petersburg 197110, RussiaSt Petersburg Inst Bioregulat & Gerontol, St Petersburg 197110, Russia
Gutop, E. O.
Linkova, N. S.
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St Petersburg Inst Bioregulat & Gerontol, St Petersburg 197110, Russia
Belgorod State Natl Res Univ, Belgorod 308015, RussiaSt Petersburg Inst Bioregulat & Gerontol, St Petersburg 197110, Russia
Linkova, N. S.
Kozhevnikova, E. O.
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St Petersburg Inst Bioregulat & Gerontol, St Petersburg 197110, RussiaSt Petersburg Inst Bioregulat & Gerontol, St Petersburg 197110, Russia
Kozhevnikova, E. O.
Fridman, N. V.
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St Petersburg Inst Bioregulat & Gerontol, St Petersburg 197110, RussiaSt Petersburg Inst Bioregulat & Gerontol, St Petersburg 197110, Russia
Fridman, N. V.
Ivko, O. M.
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St Petersburg Inst Bioregulat & Gerontol, St Petersburg 197110, RussiaSt Petersburg Inst Bioregulat & Gerontol, St Petersburg 197110, Russia
Ivko, O. M.
Khavinson, V. Kh.
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St Petersburg Inst Bioregulat & Gerontol, St Petersburg 197110, Russia
Russian Acad Sci, Pavlov Inst Physiol, St Petersburg 199034, RussiaSt Petersburg Inst Bioregulat & Gerontol, St Petersburg 197110, Russia