Several candidate drugs for Alzheimer's disease have failed to improve cognition in human clinical trials. One reason could be that they worsen neuronal defects, at least in mice.

The drugs are antibodies that have been designed to bind to and reduce levels of amyloid-β protein, which builds up in the brains of people with Alzheimer's. Marc Aurel Busche and Arthur Konnerth at the Technical University of Munich in Germany and their colleagues used high-resolution imaging of mouse brains to monitor how the antibodies affect neuronal activity. In two mouse models of Alzheimer's, two different antibodies increased the number of cells in the cortex that were electrically hyperactive, further impairing brain function, compared with untreated animals.

The results suggest a greater need to test how molecular therapies affect neuronal function in the brains of living animals, the authors say.

Nature Neurosci. http://dx.doi.org/10.1038/nn.4163 (2015)