A growing body of evidence implicates low membrane cholesterol in the pathogenesis of Alzheimer’s disease (AD). Here we show that A 42 soluble oligomers accumulate more slowly and in reduced amount at the plasma membranes of PS-1L392V and APPV717I fibroblasts from familial AD (FAD) patients enriched in cholesterol content than at the counterpart membranes. The A 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 42 oligomer accumulation at the cell surfaces and to the following A 42-induced cell death in AD neurons.

Membrane cholesterol enrichment prevents Abeta-induced oxidative stress in Alzheimer's fibroblasts / A. Pensalfini ; M. Zampagni ; G. Liguri ; M. Becatti ; E. Evangelisti ; C. Fiorillo ; S. Bagnoli ; E. Cellini ; B. Nacmias ; S. Sorbi ; C. Cecchi. - In: NEUROBIOLOGY OF AGING. - ISSN 0197-4580. - STAMPA. - 32:(2011), pp. 210-222. [10.1016/j.neurobiolaging.2009.02.010]

Membrane cholesterol enrichment prevents Abeta-induced oxidative stress in Alzheimer's fibroblasts.

PENSALFINI, ANNA;ZAMPAGNI, MARIAGIOIA;LIGURI, GIANFRANCO;BECATTI, MATTEO;EVANGELISTI, ELISA;FIORILLO, CLAUDIA;BAGNOLI, SILVIA;CELLINI, ELENA;NACMIAS, BENEDETTA;SORBI, SANDRO;CECCHI, CRISTINA
2011

Abstract

A growing body of evidence implicates low membrane cholesterol in the pathogenesis of Alzheimer’s disease (AD). Here we show that A 42 soluble oligomers accumulate more slowly and in reduced amount at the plasma membranes of PS-1L392V and APPV717I fibroblasts from familial AD (FAD) patients enriched in cholesterol content than at the counterpart membranes. The A 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 42 oligomer accumulation at the cell surfaces and to the following A 42-induced cell death in AD neurons.
2011
32
210
222
A. Pensalfini ; M. Zampagni ; G. Liguri ; M. Becatti ; E. Evangelisti ; C. Fiorillo ; S. Bagnoli ; E. Cellini ; B. Nacmias ; S. Sorbi ; C. Cecchi...espandi
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Utilizza questo identificatore per citare o creare un link a questa risorsa: https://hdl.handle.net/2158/387109
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