Alzheimer’s protein can sneak into the brain from the blood | Science News for Students

Alzheimer’s protein can sneak into the brain from the blood

Amyloid-beta proteins form sticky clumps in diseased brains, but may not start out there
Dec 13, 2017 — 6:45 am EST
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People with Alzheimer’s disease show physical changes to their brains. One of them is the buildup of clumps of a protein called amyloid-beta. In this image of a mouse brain, the protein clumps are red and brain cells are green.

Strittmatter Laboratory/Yale University

One hallmark of Alzheimer’s disease is clumps of a misbehaving protein in the brain. But some of that protein might not have started in the brain. Experiments on mice now show that Alzheimer’s proteins can build up in the brain after sneaking in from the blood.

Alzheimer’s is an incurable disease. It usually strikes in old age and causes symptoms such as confusion and memory loss. Researchers aren’t sure exactly what causes the brain disease. But they know that the brains of affected people have sticky protein clumps, called plaques (PLAKS). The protein that forms these clumps is known as amyloid-beta (A-beta).

The new results suggest A-beta that forms outside the brain may play some role to Alzheimer’s disease, says Mathias Jucker. He’s a neurobiologist at the University of Tübingen in Germany who did not take part in the tests. Treating a person’s brain is difficult. But this finding may help scientists develop new treatments that target easier-to-reach parts of the body — perhaps including the bloodstream. 

Extreme blood sharing

To be sure, cells in the brain make A-beta. But blood platelets, skin cells, muscles and other body parts do too. These other sites make it in small amounts. Researchers wondered whether, over time, blood might carry A-beta from those other sites into the brain, where it could collect.

Earlier studies in animals showed that A-beta injected into the bloodstream can enter the brain. But scientists didn’t know whether enough of this A-beta gets to the brain to do damage.

To test this idea, an international team of researchers performed tests using a form of extreme blood sharing. They used six pairs of mice. Each pair had one normal mouse. The second animal was a mutant. It carried some altered gene to make lots of human A-beta protein. Researchers surgically joined the mice so that blood flowed between those in each pair. And they continued to share each other’s blood for a year.

Afterward, brains of the mutant mice were full of A-beta plaques. That’s what researchers expected. But they also found plaques inside the brains of the normal mice in each joined pair.

Story continues below image.

brain plaques
Brain tissue from normal, healthy mouse (left) shows no sign of plaque (triangles) or A-beta (arrows). Both were seen in brains of a mutant mouse (such as right image) and to a lesser degree in a mouse that shared its blood (middle image).
X.-L. Bu et al/Molecular Psychiatry 2017

The normal mice didn’t have as much A-beta in their brains. Still, the fact that they had any plaques was notable, says Weihong Song. He’s a neuroscientist in Canada at the University of British Columbia in Vancouver. He was also part of the group that conducted the experiments.

Other mice had no mutation and shared no blood with others. These control mice served as comparisons, showing what normal healthy mice should look like. And they had no protein clumps in their brains.

Song's team published its findings online October 31 in Molecular Psychiatry.

Brains of the joined mice showed other signs of damage. The researchers saw inflammation and tiny areas of bleeding in the brains of normal mice that had shared blood containing lots of A-beta. The brains of these mice also contained a dangerous type of a protein known as tau. Both A-beta plaques and tangles of tau protein show up in the brains of people with Alzheimer’s disease.

Out of balance

The new results don’t mean that protein hitchhikers in blood cause Alzheimer’s disease. “We still think of Alzheimer’s as a brain disorder,” Song says. But in some cases, factors in the blood might nudge the disease along.

Normally, “there is a balance between A-beta inside and outside the brain,” he says. But this balance can be thrown off. The body may be chock-full of the protein. Or the blood-brain barrier — the blockade that keeps potential hazards out of the brain — may weaken with age. In any of these cases, the brain may get an extra dose, Song thinks. It’s possible that drugs, or treatments that reduce A-beta in the body, could tweak this balance in the right direction. And that might help slow or prevent Alzheimer’s disease. 

The experiments don’t suggest that people can get Alzheimer’s from another person’s blood says John Collinge. He’s a neurologist at University College London, in England. “There really isn’t any evidence that you can transmit Alzheimer’s disease by blood transfusion,” he says. So this study is informative, he says, “but shouldn’t cause alarm.”

Power Words

(for more about Power Words, click here)

Alzheimer’s disease     An incurable brain disease that can cause confusion, mood changes and problems with memory, language, behavior and problem solving. No cause or cure is known.

amyloid-beta     A protein fragment that can build to high levels in the brains of people who have Alzheimer’s disease. Over time, this material can lead to localized cell death.

blood-brain barrier     A barrier of tightly packed cells that carefully regulate what molecules can — and can’t — enter the brain. The barrier protects the brain from foreign substances in the blood and helps to maintain a constant environment for brain cells.

cell     The smallest structural and functional unit of an organism. Typically too small to see with the unaided eye, it consists of a watery fluid surrounded by a membrane or wall. Depending on their size, animals are made of anywhere from thousands to trillions of cells. Most organisms, such as yeasts, molds, bacteria and some algae, are composed of only one cell.

control     A part of an experiment where there is no change from normal conditions. The control is essential to scientific experiments. It shows that any new effect is likely due only to the part of the test that a researcher has altered. For example, if scientists were testing different types of fertilizer in a garden, they would want one section of it to remain unfertilized, as the control. Its area would show how plants in this garden grow under normal conditions. And that gives scientists something against which they can compare their experimental data.

disorder     (in medicine) A condition where the body does not work appropriately, leading to what might be viewed as an illness. This term can sometimes be used interchangeably with disease.

factor     Something that plays a role in a particular condition or event; a contributor.

gene     (adj. genetic) A segment of DNA that codes, or holds instructions, for a cell’s production of a protein. Offspring inherit genes from their parents. Genes influence how an organism looks and behaves.

inflammation     (adj. inflammatory) The body’s response to cellular injury and obesity; it often involves swelling, redness, heat and pain. It also is an underlying feature responsible for the development and aggravation of many diseases, especially heart disease and diabetes.

mutation     (adj. mutant) Some change that occurs to a gene in an organism’s DNA. Some mutations occur naturally. Others can be triggered by outside factors, such as pollution, radiation, medicines or something in the diet. A gene with this change is referred to as a mutant.

neurobiologist     Scientist who studies cells and functions of the brain and other parts of the nervous system.

neurology     A research field that studies the anatomy and function of the brain and nerves. People who work in this field are known as neurologists (if they are medical doctors) or neuroscientists if they are researchers with a PhD.

neuroscientist     Someone who studies the structure or function of the brain and other parts of the nervous system.

online     (n.) On the internet. (adj.) A term for what can be found or accessed on the internet.

plaque     An accumulation of materials in the body from the fluids that move through an area or bathe it. They can be minerals, proteins or other substances that collect as deposits.

platelets     The smallest of blood cells, their role is to hunt for signs that a blood vessel has been damaged. Then the platelets congregate at the site of damage and transform themselves, growing long tentacles. There, they link together, creating a clot to plug any hole. This should help stem the potential loss of blood.

protein     A compound made from one or more long chains of amino acids. Proteins are an essential part of all living organisms. They form the basis of living cells, muscle and tissues; they also do the work inside of cells. Among the better-known, stand-alone proteins are the hemoglobin (in blood) and the antibodies (also in blood) that attempt to fight infections. Medicines frequently work by latching onto proteins.

psychiatry     A field of medicine where doctors study and treat diseases of the human mind. Treatments may consist of talking therapies, prescription drugs or both. People who work in this field are known as psychiatrists.

symptom     A physical or mental indicator generally regarded to be characteristic of a disease. Sometimes a single symptom — especially a general one, such as fever or pain — can be a sign of any of many different types of injury or disease.

transfusion     (v. transfuse) The transfer of donated blood or blood products into the circulatory system of a person or animal.

transmit     (n. transmission) To send or pass along.

Citation

X-L Bu et al. Blood-derived amyloid-β protein induces Alzheimer’s disease pathologies. Molecular Psychiatry. Published online October 31, 2017. doi: 10.1038/mp.2017.204.