The amyloid-β peptide binds to cyclin B1 and increases human cyclin-dependent kinase-1 activity

The pathological features of Alzheimer's disease include deposition of amyloid-β (Aβ) containing plaques and increases in the expression of cyclin-dependent kinase (CDK) enzymes. Chemical inhibition of CDKs prevents the neurotoxicity of the Aβ peptide. The activity of these kinases requires the binding of a cyclin component to the catalytic enzyme component. This study characterizes direct interactions between Aβ and cyclin B1. Aβ fragments containing the cytotoxic 31-35 region could inhibit biotinylated Aβ binding to cyclin B1. The same cytotoxic Aβ fragments all increased CDK-1 phosphorylation of known substrates in a cell free system. The CDK-1 inhibitor olomoucine prevented the cytotoxicity of Aβ 31-35 containing peptides in differentiated human teratocarcinoma cell line, Ntera 2/cl-D1 (NT-2) neurons. These direct interactions between cyclin B1 and Aβ provide potential mechanisms for the cytotoxicity of the Aβ peptide.