Transforming growth factor β2 autocrinally mediates neuronal cell death induced by amyloid-β

Amyloid beta (A beta), the major component of the senile plaques of Alzheimer's disease, is implicated in neuronal cell death. We have found that A beta 42, a neurotoxic form of A beta peptide, induces both neuronal and glial expression of TGF beta 2. We have further demonstrated that the addition into culture media of neutralizing antibody to TGF beta 2 or a large amount of the recombinant soluble amyloid precursor protein alpha, the extracellular domain of amyloid precursor protein (APP) generated by a. secretase, suppresses death in primary cortical neurons (PCNs) induced by A beta 42 in vitro. Combined with the finding in our recent study indicating that TGF beta 2 is a neuronal cell death-inducing ligand for APP, it is suggested that TGF beta 2 is an autocrinal mediator for A beta 42-induced death in PCNs. (c) 2006 Wiley-Liss, Inc.