Differences in How Proteins Spread in Brain May Explain Increase in Alzheimer’s Risk With Age, Mouse Study Suggests

Marisa Wexler, MS avatar

by Marisa Wexler, MS |

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Differences in how proteins move in the brain at older ages may explain why the risk of Alzheimer’s disease increases with age, according to a new study in mice.

The study, “Experimental evidence for the age dependence of tau protein spread in the brain,” was published in the journal Science Advances.

It’s a well-known fact that older people are more likely to develop Alzheimer’s. But why exactly is that?

One hypothesis is that older brains allow pathological, or disease-causing proteins to spread more easily.

Researchers note that there are two types of protein “clumps” known to be present in Alzheimer’s brains: amyloid beta plaques and tau neurofibrillary tangles. While both are involved in the development of Alzheimer’s, the emergence of the tau proteins reflects disease progression.

These proteins are believed to spread along nerve cells from one to another. This might explain, at least in part, how the disease progresses, affecting more and more parts of the brain.

To find out whether tau proteins can spread more easily in aged brains, a team led by Susanne Wegmann, PhD, of the German Center for Neurodegenerative Diseases, turned to gene vectors — modified viruses that deliver foreign DNA into cells. The researchers used the gene vectors to engineer the brains of old and young mice to express human tau protein in one brain region. Then, they observed how the protein spread through the brains of animals of different ages.

“Human tau proteins spread about twice as fast in older mice as compared to younger animals,” Wegmann, a study co-author, said in a press release.

Importantly, human tau protein is normally present in healthy brains — it’s only when it folds incorrectly, and clumps up, that problems are thought to occur. The researchers noted that whether such clumps are a cause or a symptom of Alzheimer’s is a matter of some debate. Thus, the investigators also looked at how both normal and misfolded tau proteins spread throughout the brain.

“It has long been thought that it is primarily the pathological [misfolded] form of tau that passes from one cell to the next,” Wegmann said. “However, our results show that the healthy version of the protein also propagates in the brain and that this process increases in old age. Cells could also be harmed by receiving and accumulating large amounts of healthy tau.”

Now, the investigators say, even more questions are in need of answering. Specifically, the researchers now want to determine what are the underlying biological reasons that tau proteins spread more quickly in older brains. Additional studies will be needed to fully understand these processes. Researchers hope that greater understanding will eventually allow for better care and treatment of Alzheimer’s disease.