Scientists have long thought that Alzheimer's disease originates in the brain, but new research suggests that a key protein that triggers the disease could be carried to the brain from elsewhere in the body. The research offers pathways to new drug therapies that could potentially stop or slow the disease without working directly on the brain.
One of the fundamental symptomatic causes of Alzheimer's disease is an accumulation, or "clumping", of amyloid beta proteins in the brain. These accumulations are called amyloid plaques and they smother brain cells, resulting in inhibited nerve function and impaired memory.
Several promising recent studies have shown the potential for an early-warning diagnostic blood test to be developed that identifies the build-up of these amyloid beta proteins in the bloodstream. But until now it was generally considered that the plaque-generating proteins responsible for Alzheimer's were produced inside the brain.
A new study from Chinese and Canadian scientists shows that amyloid beta proteins produced in other parts of the body can in fact cross into the brain and contribute to Alzheimer's-like symptoms.
The process was identified using a technique called parabiosis, where two separate organisms are surgically attached to share the same bloodstream. The researchers joined a normal mouse with a partner that was genetically modified to produce high levels of the amyloid beta protein.
After 12 months of connected blood circulation the normal mice connected had effectively "contracted" Alzheimer's disease from their genetically-modified partner. The proteins had traveled into the brains of the normal mice and developed into plaques causing a variety of Alzheimer's-like symptoms. Effects were noticed in the healthy mice after as little as four months.
The researchers suggest that this is the first proof that amyloid beta produced outside of the brain can in fact contribute to the disease. Outside of the brain, amyloid beta is also produced in muscles, blood platelets and blood vessels. The hypothesis is that as we get older more amyloid beta crosses into the brain, amplifying the degenerative aspects of Alzheimer's.
"The blood-brain barrier weakens as we age," says Weihong Song from the University of British Columbia. "That might allow more amyloid beta to infiltrate the brain, supplementing what is produced by the brain itself and accelerating the deterioration."
The study suggest that drug therapies could be developed to target amyloid beta in the body and push it towards the kidneys or liver to clear it from a system before it can accumulate in the brain, which is a difficult target for drug treatments.
The research was published in the journal Molecular Psychiatry.
Source: University of British Columbia
