Document Type




Publication Date



Public Library of Science

Source Publication

PLoS Biology

Source ISSN


Original Item ID

doi: 10.1371/journal.pone.0011820


The mechanisms that induce Alzheimer’s disease (AD) are largely unknown thereby deterring the development of disease-modifying therapies. One working hypothesis of AD is that Aβ excess disrupts membranes causing pore formation leading to alterations in ionic homeostasis. However, it is largely unknown if this also occurs in native brain neuronal membranes. Here we show that similar to other pore forming toxins, Aβ induces perforation of neuronal membranes causing an increase in membrane conductance, intracellular calcium and ethidium bromide influx. These data reveal that the target of Aβ is not another membrane protein, but that Aβ itself is the cellular target thereby explaining the failure of current therapies to interfere with the course of AD. We propose that this novel effect of Aβ could be useful for the discovery of anti AD drug capable of blocking these "Aβ perforates". In addition, we demonstrate that peptides that block Aβ neurotoxicity also slow or prevent the membrane-perforating action of Aβ.


Published version. PLoS Biology, Vol. 5, No. 7 (July 2010): e11820. DOI. © 2010 Public Library of Science. Published under Creative Commons License CC BY 4.0.

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