FIGHTING ALZHEIMER’S
UBC study opens doors
A new study from UBC has found that toxic proteins associated with Alzheimer’s disease produced outside the brain can trigger the disease inside the brain, a discovery that opens the door to a whole new approach to treatment.
Rather than therapies targeting the brain — which is protected by a difficult-to-penetrate membrane called the blood-brain barrier — scientists can turn their attention to clearing the proteins from the rest of the body as a way to stop or slow the onset of the disease.
The study by UBC psychiatry professor Weihong Song and neurology professor Wang Yan-jiang at Third Military Medical University in Chongqing was published in the journal Molecular Psychiatry.
Amyloid-beta protein is produced in the brain where it forms sticky clumps or plaques that damage brain cells, interfere with their function, trigger inflammation and lead to cell death. As brain cells lose the ability to function, learning and memory are impaired.
Those proteins are also produced in cells elsewhere in the body and travel to the brain, through the fortress-like bloodbrain barrier, where they contribute to the development of the disease, said Song.
As we age, the barrier becomes more porous, allowing amyloidbeta to pass more easily to the brain.
But the concentration of amyloid-beta also appears to stay in balance across the blood-brain barrier, making it possible to reduce their concentration inside the brain by removing the proteins from the rest of the body.
“Clearance of amyloid outside the brain could help reduce the amyloid load inside the brain and might help slow down the disease progression,” Song said. Drugs that mark the protein in a way that is recognizable to the kidney or liver could rid the blood of the protein before it ever reaches the brain.
After decades of research, there is no approved drug treatment that can remove or destroy amyloid-beta inside the brain.
An experimental treatment that is supposed to bind to amyloid proteins inside the brain produced by Eli Lilly failed its clinical trial last year. That company has spent $3 billion over more than 25 years on developing drugs for Alzheimer’s.
Merck shut down trials earlier this year for another drug that was designed to interfere with the creation of amyloid-beta inside the brain.
About 750,000 Canadians have Alzheimer’s, according to the Alzheimer’s Association.
To demonstrate the cancer-like mobility of amyloid-beta, Song and Wang surgically attached mice in pairs, one healthy and the other modified to produce high levels of amyloid-beta.
While sharing a blood supply, the normal mice showed Alzheimer’s symptoms after blood-borne amyloid proteins from the modified mice passed through their blood-brain barriers and damaged their brain cells.
The normal mice developed plaques inside the brain and protein tangles that kill brain cells from the inside out, as well as brain cell degeneration, inflammation and micro-bleeds common in Alzheimer’s.
Electrical signals involved in learning and memory were impaired after just four months.