Like our bodies, our brains have their own waste disposal system. Until recently, it was thought that one of the brain’s key waste disposal systems did not function properly in Alzheimer’s patients, allowing mutant proteins to accumulate in the brain.
Plaques (red) in the brains of mice with Alzheimer’s disease.
Photo: Willem Kamphuis, Netherlands Institute for Neuroscience.
But the reality is much more complicated, according to researcher Elly Hol's group at the Netherlands Institute for Neuroscience. The group’s findings offer guideposts for follow-up research, focused on slowing the progress of Alzheimer’s in patients.
In addition to her position with the Academy’s Netherlands Institute for Neuroscience, Professor Elly Hol also has an appointment with the University of Amsterdam. Her group's findings have just been published in the journal Brain.
The role of proteins
Proteins play an important role in our cells. They ensure that countless chemical reactions take place smoothly. Proteins may consist of thousands of amino acids that fold up into a small package. The protein’s function depends on the shape of the package to some extent. If a protein is folded incorrectly, it forms a useless molecule that has to be cleared away by the brain’s waste disposal system.
We know that in Alzheimer’s patients, an incorrectly folded protein, amyloid-β, builds up in the brain. The build-up is referred to as a plaque. These plaques are surrounded by damaged nerve cells. Until now, researchers thought that a malfunction of the brain’s waste disposal system rendered it incapable of clearing away the build-up of amyloid-β in Alzheimer’s patients.
Contrary to this assumption, Elly Hol’s group has shown that the brain’s waste disposal system is in fact activated in Alzheimer’s patients, and that it is also involved in an inflammatory response around the plaques. Researchers differ as to whether the inflammatory response is a good thing – because it assists recovery– or a bad thing – because it too causes damage. The research suggests new approaches to reducing the inflammatory response in the brain. Further research will have to demonstrate whether a new approach can ultimately help slow the progress of Alzheimer’s disease.
- Orre, M., Kamphuis, W., Dooves, S., Kooijman, L., Chan, E.T., Kirk, C.J., Dimayuga Smith, V., Koot, S., Mamber, C., Jansen, A.H., Ovaa, H., and Hol, E.M. Reactive glia show increased immunoproteasome activity in Alzheimer's disease. Brain [abstract]