Altered protein phosphorylation as a resource for potential AD biomarkers

The amyloidogenic peptide, A beta, provokes a series of events affecting distinct cellular pathways regulated by protein phosphorylation. A beta inhibits protein phosphatases in a dose-dependent manner, thus it is expected that the phosphorylation state of specific proteins would be altered in response to A beta. In fact several Alzheimer's disease related proteins, such as APP and TAU, exhibit pathology associated hyperphosphorylated states. A systems biology approach was adopted and the phosphoproteome, of primary cortical neuronal cells exposed to A beta, was evaluated. Phosphorylated proteins were recovered and those whose recovery increased or decreased, upon A beta exposure across experimental sets, were identified. Significant differences were evident for 141 proteins and investigation of their interactors revealed key protein clusters responsive to A beta treatment. Of these, 73 phosphorylated proteins increased and 68 decreased upon A beta addition. These phosphorylated proteins represent an important resource of potential AD phospho biomarkers that should be further pursued.