beta-amyloid peptide-induced apoptosis regulated by a novel protein containing a G protein activation module

Degeneration of neurons in Alzheimer's disease is mediated by beta -amyloid peptide by diverse mechanisms, which include a putative apoptotic componen t stimulated by unidentified signaling events. This report describes a nove l beta -amyloid peptide-binding protein (denoted BBP) containing a G protei n-coupling module. BBP is one member of a family of three proteins containi ng this conserved structure. The BBP subtype bound human beta -amyloid pept ide in vitro with high affinity and specificity. Expression of BBP in cell culture induced caspase-dependent vulnerability to beta -amyloid peptide to xicity. Expression of a signaling-deficient dominant negative BBP mutant su ppressed sensitivity of human Ntera-2 neurons to beta -amyloid peptide medi ated toxicity. These findings suggest that BBP is a target of neurotoxic be ta -amyloid peptide and provide new insight into the molecular pathophysiol ogy of Alzheimer's disease.