Soluble oligomeric Aβ disrupts the protein kinase C signaling pathway

Alzheimer's disease (AD) is characterized by selective neuro-degeneration of neurons involved in cognitive function. Current hypothesis for AD etiology needs to be reconsidered because fibrillar Aβ cannot explain selective neurodegeneration. Recent evidence suggests oligomeric Aβ may be more relevant to AD etiology. Here we show signaling disruption induced by oligomeric Aβ. Using the MTT assay, NT2 showed greatest susceptibility to soluble oligomeric Aβ. In the kinase assay, treatment with either monomeric Aβ or fibrillar Aβ evoked no response in PKA, PKC and TK. Oligomeric Aβ treatment, however, inactivated membranous PKC but activated cytosolic PKC in NT2 within 24 h. Our data suggest that oligomeric Aβ may cause selective neurodegeneration through a PKC signaling, distinctive from fibrillar Aβ.