Alzheimer's: Protein from outside the brain may be involved

Scientists find that amyloid beta can permeate the blood-brain barrier to give rise to Alzheimer's disease.

A study in mice has discovered that amyloid beta, the protein that causes one of the hallmarks of Alzheimer's disease in the brain, may also come from other parts of the body.

In the journal Molecular Psychiatry, researchers describe how they surgically attached mice to each other for several months to show that amyloid beta in the bloodstream can enter the brain and cause symptoms of Alzheimer's disease.

If the study findings are true of humans, then the team hopes that they might lead to drugs that do not have to target the brain, which is difficult to reach and treat. It might be easier eliminate the protein before it reaches the brain — for example, by targeting the liver or kidneys instead.

As co-senior researcher Weihong Song, a professor of psychiatry at the University of British Columbia in Canada, explains, "The blood-brain barrier weakens as we age. That might allow more amyloid beta to infiltrate the brain, supplementing what is produced by the brain itself and accelerating the deterioration."

Alzheimer's disease is the most common form of dementia, which is a brain-wasting disorder that progressively destroys people's ability to reason, remember, communicate, and take care of themselves.

Although there is a type of Alzheimer's that can strike younger people, it is more common in those aged 60 and older.

Amyloid beta and plaques

Of the 47 million people worldwide with dementia, approximately 65 percent are thought to have Alzheimer's disease.

In the United States, there are around 5 million people living with Alzheimer's disease, and this number is projected to reach 14 million by 2050.

The exact cause of Alzheimer's is not yet clear. Experts generally believe that there are several causes and that they arise differently in different people.

A prominent hallmark of the disease is the presence in the brain of sticky, abnormal deposits of amyloid beta protein. As the deposits — also known as plaques — increase, they disrupt brain cells and their connections to each other, and eventually the brain cells die.

Amyloid beta comes from a larger protein that is found not only in the brain but also in other organs. It is also produced in blood platelets, muscles, and blood vessels. 

Plaques and 'tangles'

In their study report, the researchers explain that because of the blood-brain barrier, there has been a general belief that the amyloid beta that causes the brain plaques found in Alzheimer's disease originates only in the brain. This view, however, has never been tested.

For their study, the team engineered mice to carry a version of a human gene that produces high levels of amyloid beta and surgically attached them — in a method called "parabiosis" — to normal "wild-type" mice.

After a period of 12 months, the normal mice had developed Alzheimer's disease, including the accumulation of plaques of amyloid beta between brain cells.

The team also found that some of the animals' brain cells contained features similar to "tangles," or twisted strands of protein, which are another hallmark of Alzheimer's disease. These tangles also kill brain cells.

There were also other signs of Alzheimer's disease, such as the degeneration of brain cells, small bleeds, and inflammation.

Also, after only 4 months of being joined to the mice carrying the mutated gene, the normal mice's brains were already showing disruptions to the electrical signals that carry information between the cells.

Prof. Song says that the amyloid beta had traveled from the mice with the mutated gene through the bloodstream to the brains of the normal mice.

"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."

Prof. Weihong Song

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