One of the first symptoms of Alzheimer's disease is the hyperactivity of the neuronal networks in the brain. This is evident, for example, by an increase in epileptic seizures in people who later develop Alzheimer's disease. Researchers also see 'epileptiform activity' in young animals in mouse models, even before the disease manifests itself. "This indicates that hyperactivity is an important first characteristic of the disease," says last author Corette Wierenga. It was already known that an increase of the protein amyloid β plays a role in this. A high concentration of this protein is harmful and makes the brain cells hyperactive. However, it was unclear how this happens exactly and how it can explain the hyperactivity in the early stages of the disease. In this research the scientists studied the effect of amyloid β-protein by looking at the inhibitory electrical currents in brain material treated with this protein. This showed that these electrical currents were disturbed and decreased by the amyloid β-protein. The researchers also saw this decrease in mice that produce too much amyloid β themselves. They also discovered that the inhibitory brain connections – so-called inhibitory synapses – on the extensions of the nerve cells are considerably more sensitive to the amyloid β-protein than inhibitory synapses on the cell bodies. "These dendritic inhibitory synapses ensure that the different synaptic signals are correctly integrated and interpreted by the brain cells. A disruption of this integration process can lead to disturbed activity of brain cells", Wierenga explains.