Antipodal Effects of p25 on Synaptic Plasticity, Learning, and Memory—Too Much of a Good Thing Is Bad

Elevated activity of the Cdk5/p25 complex has been implicated in the pathogenesis of Alzheimer's disease. The report by Fischer and colleagues in this issue of Neuron describes a dichotomous role for the activator protein p25 in synaptic plasticity, learning, and memory, whereby transient expression in transgenic mice produces beneficial effects, but prolonged expression is detrimental. This work demonstrates the complexity of Cdk5/p25 in neuronal function and shows that dysregulation of a factor involved in plasticity can cause neurodegeneration.