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

Amyloid β (Aβ), the major component of the senile plaques of Alzheimer's disease, is implicated in neuronal cell death. We have found that Aβ42, a neurotoxic form of Aβ peptide, induces both neuronal and glial expression of TGFβ2. We have further demonstrated that the addition into culture media of neutralizing antibody to TGFβ2 or a large amount of the recombinant soluble amyloid precursor protein α, the extracellular domain of amyloid precursor protein (APP) generated by α secretase, suppresses death in primary cortical neurons (PCNs) induced by Aβ42 in vitro. Combined with the finding in our recent study indicating that TGFβ2 is a neuronal cell death-inducing ligand for APP, it is suggested that TGFβ2 is an autocrinal mediator for Aβ42-induced death in PCNs.