CHANNEL FORMATION IN PLANAR LIPID BILAYERS BY A NEUROTOXIC FRAGMENT OF THE BETA-AMYLOID PEPTIDE

Alzheimer's disease (AD) pathology is characterized by plaques, tangle s, and neuronal cell loss. The main constituent of plaques is beta-amy loid peptide (A beta), a 39-42 residue peptide which has been linked t o disruption of calcium homeostasis and neurotoxicity in vitro. We dem onstrate that a neurotoxic fragment of A beta, A beta (25-35) spontane ously inserted into planar lipid membranes to form weakly selective, v oltage dependent, ion-permeable channels. We suggest that channel form ation may be involved in the pathogenesis of AD and that A beta (25-35 ) may be the active channel forming segment. (C) 1994 Academic Press, Inc