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

Amyloid b (Ab), the major component of the senile plaques of Alzheimer’s disease, is implicated in neuronal cell death. We have found that Ab42, a neurotoxic form of Ab peptide, induces both neuronal and glial expression of TGFb2. We have further demonstrated that the addition into culture media of neutralizing antibody to TGFb2 or a large amount of the recombinant soluble amyloid precursor protein a, the extracellular domain of amyloid precursor protein (APP) generated by a secretase, suppresses death in primary cortical neurons (PCNs) induced by Ab42 in vitro. Combined with the finding in our recent study indicating that TGFb 2i s a neuronal cell death-inducing ligand for APP, it is suggested that TGFb2 is an autocrinal mediator for Ab42induced death in PCNs. V V C 2006 Wiley-Liss, Inc.