Channel formation in planar lipid bilayers by a neurotoxic fragment of the beta-amyloid peptide.

Alzheimer's disease (AD) pathology is characterized by plaques, tangles, and neuronal cell loss. The main constituent of plaques is beta-amyloid peptide (A beta), a 39-42 residue peptide which has been linked to disruption of calcium homeostasis and neurotoxicity in vitro. We demonstrate that a neurotoxic fragment of A beta, A beta (25-35) spontaneously inserted into planar lipid membranes to form weakly selective, voltage dependent, ion-permeable channels. We suggest that channel formation may be involved in the pathogenesis of AD and that A beta (25-35) may be the active channel forming segment.