β-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 component stimulated by unidentified signaling events. This report describes a novel beta -amyloid peptide-binding protein (denoted BBP) containing a G protein-coupling module. BBP is one member of a family of three proteins containing this conserved structure. The BBP subtype bound human beta -amyloid peptide in vitro with high affinity and specificity. Expression of BBP in cell culture induced caspase-dependent vulnerability to beta -amyloid peptide toxicity. Expression of a signaling-deficient dominant negative BBP mutant suppressed sensitivity of human Ntera-2 neurons to beta -amyloid peptide mediated toxicity. These findings suggest that BBP is a target of neurotoxic beta -amyloid peptide and provide new insight into the molecular pathophysiology of Alzheimer's disease.