نتایج یک پژوهش: آلزایمر منشاء مغزی ندارد؛ آلزایمر بیماری همهٔ بدن

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.

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

 Alzheimer’s disease might be a “whole body” problem

Alzheimer’s disease, the leading cause of dementia, has long been assumed to originate in the brain. But research from the University of British Columbia and Chinese scientists indicates that it could be triggered by breakdowns elsewhere in the body.

The findings, published today in Molecular Psychiatry, offer hope that future drug therapies might be able to stop or slow the disease without acting directly on the brain, which is a complex, sensitive and often hard-to-reach target. Instead, such drugs could target the kidney or liver, ridding the blood of a toxic protein before it ever reaches the brain.

The scientists demonstrated this cancer-like mobility through a technique called parabiosis: Surgically attaching two specimens together so they share the same blood supply for several months.

A pair of surgically-joined mice.

UBC Psychiatry Professor Weihong Song and Neurology Professor Yan-Jiang Wang at Third Military Medical University in Chongqing attached normal mice, which don’t naturally develop Alzheimer’s disease, to mice modified to carry a mutant human gene that produces high levels of a protein called amyloid-beta. In people with Alzheimer’s disease, that protein ultimately forms clumps, or “plaques,” that smother brain cells.

Normal mice that had been joined to genetically modified partners for a year “contracted” Alzheimer’s disease. Dr. Song says the amyloid-beta traveled from the genetically-modified mice to the brains of their normal partners, where it accumulated and began to inflict damage.

Not only did the normal mice develop plaques, but also a pathology similar to “tangles” – twisted protein strands that form inside brain cells, disrupting their function and eventually killing them from the inside-out. Other signs of Alzheimer’s-like damage included brain cell degeneration, inflammation and microbleeds. In addition, the ability to transmit electrical signals involved in learning and memory – a sign of a healthy brain – was impaired, even in mice that had been joined for just four months.

Besides the brain, amyloid-beta is produced in blood platelets, blood vessels and muscles, and its precursor protein is found in several other organs. But until these experiments, it was unclear if amyloid-beta from outside the brain could contribute to Alzheimer’s disease. This study, Dr. Song says, shows it can.

“The blood-brain barrier weakens as we age,” says Dr. Song, a Canada Research Chair in Alzheimer’s Disease and the Jack Brown and Family Professor. “That might allow more amyloid beta to infiltrate the brain, supplementing what is produced by the brain itself and accelerating the deterioration.”

Dr. Song, head of UBC’s Townsend Family Laboratories, envisions a drug that would bind to amyloid-beta throughout the body, tagging it biochemically in such a way that the liver or kidneys could clear it.

“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,” he says