It is believed that a rogue protein originating elsewhere in the body could be responsible
Scientists believe a rogue protein strongly linked to the disorder may appear elsewhere in the body before breaking through the brain’s natural defences.
If the theory is right, it could have huge implications for diagnosing and treating the disease.
New therapies could target the amyloid-beta protein and clear it from the body before it spreads to the brain.
The protein accumulates in sticky clumps, or plaques, in the brains of Alzheimer’s patients but can also be present in blood platelets, blood vessels, and muscles.
In addition the precursor molecule from which it is derived can be found in several organs.
There has been no evidence that amyloid-beta from outside the brain causes Alzheimer’s, until now
We need to pay attention to the whole body to understand where it comes from and how to stop it
Until now there has been no clear evidence to show that amyloid-beta from outside the brain plays a role in Alzheimer’s.
But experiments with mice indicate that it can travel through the blood stream before entering the brain and triggering the disease.
Lead scientist Professor Weihong Song, from the University of British Columbia, Canada, said: “Alzheimer’s disease is clearly a disease of the brain, but we need to pay attention to the whole body to understand where it comes from and how to stop it.“
The researchers studied surgically conjoined mice, one of which was normal and the other modified to carry a mutant human Alzheimer’s gene that produces high levels of amyloid-beta.
After remaining attached to their partners for a year, the normal mice developed Alzheimer’s disease.
Their brains were infected with toxic protein that had spread from the genetically modified mice via the animals’ shared blood circulation, the scientists believe.
Not only did the normal mice acquire amyloid-beta plaques, they also developed another key hallmark of Alzheimer’s – twisted protein strands within neurons known as “tau tangles”.
Other signs of Alzheimer’s-like damage included the loss of brain cells, inflammation and microbleeds.
The ability to transmit electrical signals involved in learning and memory was impaired in the normal mice after just four months.
Prof Song pointed out that the “blood-brain barrier” – a cellular “wall” that acts like an immigration checkpoint, allowing some molecules in and not others – weakens with age.
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“That might allow more amyloid-beta to infiltrate the brain, supplementing what is produced in the brain itself and accelerating the deterioration,” he said.
Developing effective drugs that overcome the blood-brain barrier is a challenge. Tackling Alzheimer’s by targeting amyloid-beta outside the brain may be a lot easier, say the scientists.
Prof Song envisioned drugs that could tag the protein biochemically to facilitate its clearance from the body by the liver and kidneys.
The research is reported in the journal Molecular Psychiatry.
Dr David Reynolds, chief scientific officer at the charity Alzheimer’s Research UK, said: “As with any research involving mice, the only way to know if these findings are relevant to how Alzheimer’s develops in people is through studies that focus on human biology.
“If these findings do prove to be relevant to people, it highlights the continued importance of developing treatments that target amyloid in the body as well as the brain.“
He added: “There is no suggestion from this research that Alzheimer’s could be spread by blood transfusions in people.
“Last year an extensive study involving 1.4 million people who were followed up for many years found no increased risk associated with receiving a transfusion from people with Alzheimer’s.“