Hyperactive Neurons Behind Failure of Immunotherapy for Alzheimer's

the Psychiatry Advisor take:

Although immunotherapies that use antibodies to target beta-amyloid therapies have been considered promising as an Alzheimer’s disease treatment based on animal studies, clinical studies involving them have not been successful. Now researchers believe the reason why may be because the treatment increases development of hyperactivity nerve cells.

Marc Aurel Busche, MD, PhD, of the Technical University of Munich, Germany, and colleagues used Alzheimer’s mice models that carry a gene for the beta-amyloid precursor protein. Researchers gave the rodents immunotherapy antibodies and subsequently analyzed the activity of nerve cells.

Although the amount of beta-amyloid plaque subsided after immunotherapy, the number of hyperactive neurons dramatically rose. These neurons are unable to perform normal functions, which may explain why the immunotherapy hasn’t shown to improve Alzheimer’s symptoms despite a decline in beta-amyloid plaque, the researchers reported in the journal Nature Neuroscience.

The researcher also found that in younger Alzheimer’s mice whose brain had yet to show the presence of beta-amyloid plaque, immunotherapy led to an increase in hyperactive neurons.

“We suspect that the mechanism is as follows: The antibodies used in treatment release increasing numbers of soluble oligomers,” Busche said in a statement. “These are precursors of the plaques and have been considered problematic for some time now. This could cause the increase in hyperactivity.”