Soluble oligomeric Aβ disrupts the protein kinase C signaling pathway

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