Can We Clear Toxic Proteins from the Brain? An Encouraging Breakthrough

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3D-rendered image of neuron cell on black background showing synapses glowing.

Research by BrightFocus grantee Matthew Campbell, PhD, of Trinity College Dublin, suggests a unique way to help clear the brain of toxic amyloid beta protein, which contributes to the development of Alzheimer’s.

A BrightFocus-funded research team has discovered a potentially new way to get Alzheimer’s medications into the brain, a long-standing challenge.  This novel process could help clear the brain of the build-up of the toxic protein known as amyloid beta (AB) that leads to Alzheimer’s.

Unlike other parts of the body’s circulation, the brain’s circulation is tightly controlled to keep out damaging substances, such as harmful chemicals and infections.  Unfortunately, this “blood-brain barrier” (BBB) also keeps medications from entering the brain.

That means that when the brain can no longer rid itself of excessive AB, then neuron-killing plaques and tangles gradually start to develop. Scientists want to get that excess AB out of the brain before it creates problems; however, because of the BBB, it’s not possible to send medications through the bloodstream to do so.

Matthew Campbell, PhD, and his colleagues at Trinity College Dublin, in a study supported by our Alzheimer’s Disease Research program, have proposed a novel way to periodically clear toxic AB out of the brain. In animal experiments, they suppressed certain so-called “tight junction” proteins that, in the space between cells, act as a sort of glue or seal keeping AB out of the bloodstream.

This suppression helped remove excess AB from the brain.  Results showed higher circulating levels of AB traveling through the BBB and into the bloodstream. In mice, this clearance of AB was associated with better performance and cognitive function.

Also important, the agent used for this purpose has already entered clinical trials for other reasons, which could speed up the process of discovery and eventual testing in humans.

“Our recent findings have highlighted the importance of understanding diseases at the molecular level,” Campbell said in statements from Trinity College.  “The concept of periodic clearance of brain amyloid-beta could hold tremendous potential for Alzheimer’s patients in the future.”

This summary is an excerpt of a longer article by Martha Taggart of BrightFocus.  She interviews Dr. Campbell, who has also conducted vision research under the BrightFocus Macular Degeneration Research program. They talk about the similarities in clearance problems occurring in both macular degeneration and Alzheimer’s disease.  See BrightFocus Funds Encouraging Breakthrough for Future Alzheimer’s Treatment.

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