The Role of Lipid Rafts in this Event

Ledesma et al. [130] have shown that AD hippocampi show a large disorganization of membrane lipid rafts and reduced plasmin activity. Raft disorganization could lead to AD due to a failure in the activation of a plasmin-mediated amyloid clearance pathway. Thus, these findings highlight the importance of correct membrane organization in the maintenance of amyloid clearance (see Fig. 10.3B).

Such hypotheses are in apparent contradiction with the idea that raft perturbation by cholesterol depletion may prevent AD by reducing the production of Ab [95,102]. The amount of cholesterol removal and the different cell types used may explain the diverse results of rafts disruption. Hence, plasmin activity was lost when cholesterol reduction was no higher than 36% in human samples. In contrast, inhibition of Ab production was observed in one case after acute removal of membrane cholesterol (60%) [102] (see Fig. 10.3B), and also in undifferentiated N2A cells [95]. From these data it is clear that the lack of proper rafts organization produces changes in different raft-mediated events that might be related to AD pathogenesis.

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