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Gene patterns may explain brain's Alzheimer's vulnerability

2:28pm Thursday 11th August 2016 content supplied byNHS Choices

"Scientists say they have discovered a possible explanation for how Alzheimer's disease spreads in the brain," The Guardian reports.

Gene patterns in specific areas may explain why the disease tends to start in these regions, before spreading through the brain.

The patterns were found in areas of healthy brains that were primed to produce certain proteins. These were also the areas that tend to succumb first to signs of Alzheimer's disease.

The researchers say this type of gene activity (gene expression) in certain parts of the brain either encourages or discourages the formation of certain types of protein.

Alzheimer's disease is characterised by the build-up of abnormal clumps of proteins, known as plaques and tangles.

The researchers theorise that the body's natural defences become less able to prevent protein build-up as cells age, and this becomes apparent first in the areas most genetically primed for protein overgrowth.

Instead of trying to block all the potential triggers for Alzheimer's disease, they say, future treatments might focus on ways to strengthen these natural defences.

However, all these possibilities lie a long way in the future.

The research may help doctors understand the development of Alzheimer's disease, but much more work needs to be done before this understanding can translate into a safe and effective treatment.

Still, anything concrete we can find about this poorly understood condition is always welcome.

Where did the story come from?

The study was carried out by researchers from Cambridge University and received no specific funding. 

It was published in the peer-reviewed journal, Science Advances.

The Guardian did a good job of explaining the science, and interviewed scientists not linked to the study to help put the results in context.

The Mail Online and The Sun's coverage was also broadly accurate, but neither paper sought out independent commentary on the study.

What kind of research was this?

This was an experimental study comparing data from healthy human brains - which had been mapped for genetic and protein expression - against data about which regions of the brain are affected in early-stage Alzheimer's disease.

What did the research involve?

Researchers used data relating to 500 samples of tissue from the post-mortems of six healthy human brains, all from people aged 24 to 57, none of whom had Alzheimer's disease.

They analysed 19,700 genes to see which affected protein expression in the brain.

They looked at four types of brain cells to compare their levels of genes that protected or promoted protein expression, and the levels of amyloid-beta and tau protein expressed in the cells.

The researchers used the data to "map" regions of the brain that were more susceptible to protein growth because of their levels of protein expression.

They then compared this map to a brain map showing where Alzheimer's disease plaques and tangles typically first appear in the brain using a diagnostic system called Braak staging.

They also looked for other factors that might affect the progress of Alzheimer's disease, such as the functioning of the immune system, measured by levels of genes associated with inflammation in different regions of the brain.

The data came from a database known as the Allen Brain Atlas, which produces 3-D digital images of gene expression in human and animal brains.

What were the basic results?

Researchers found brain nerve cells (neurones) were less likely to express genes protecting against protein build-up, and more likely to express genes promoting protein growth, compared with other brain cells (astrocytes, endothelial cells and microglia).

Neurones were also more likely to be primed to express amyloid-beta protein and tau.

When comparing brain maps, those regions of the brain in which tissues were more susceptible to protein expression correlated well with the brain regions that first show signs of Alzheimer's disease. The two brain maps looked very similar.

The researchers also found healthy brains had higher levels of genes associated with inflammatory responses, but areas of the brain vulnerable to Alzheimer's disease had lower levels of gene expression involved in autoimmune responses.

How did the researchers interpret the results?

The researchers said: "Our results identify a quantitative correlation between the histopathological staging of AD [Alzheimer's disease] and the specific expression patterns of the genes corresponding to the proteins that coaggregate in plaques and tangles."

They added that the findings related to immune response suggest inflammation is also important, meaning that, "the vulnerability of specific tissues in AD may result from the sum of a number of factors", including genetic control of protein exprssion, natural defences against protein overgrowth, and the response of the immune system.

They said their research shows the brain's vulnerability to Alzheimer's disease "decades before" the age at which the disease begins, and could lead to new treatment approaches, which "rather than trying to prevent a wide range of possible triggering events, could be based on the pharmaceutical enhancement of our natural defence mechanisms". 

Conclusion

This type of exploratory science is needed to fully understand complex diseases such as Alzheimer's, which so far have not responded well to treatment.

The more we know about how a disease begins and develops, the better chance scientists have of finding ways to treat or prevent it.

This research explores one possible contributing factor to Alzheimer's disease. It doesn't provide an early way of telling who will get it - the theory is that everyone has similar regions in their brains that are more vulnerable to protein overgrowth than other regions.

And this is not an easy option for a treatment because we don't yet know how to manipulate gene expression in a way that might prevent protein build-up in vulnerable regions.

In fact, we don't even know whether protein plaques and tangles actually cause Alzheimer's disease, or whether they are just a sign of the disease.

Scientists have been looking for a cure for Alzheimer's disease for a long time. There are many avenues of research being explored throughout the world.

The fact it has taken so long to find an effective treatment is a sign of how complicated Alzheimer's is.

This research goes some way towards explaining the complex conditions that underlie our vulnerability to brain degeneration and Alzheimer's disease in later life. 

Summary

"Scientists say they have discovered a possible explanation for how Alzheimer's disease spreads in the brain," The Guardian reports. Gene patterns in specific areas may explain why the disease tends to start...

Links to Headlines

New research hints at pattern of Alzheimer's spread in the brain. The Guardian, August 10 2016

Are we another step closer to preventing Alzheimer's? Scientists discover genes that reveal vital clues about how the disease progresses. Mail Online, August 10 2016

Alzheimer's disease researchers discover gene which could help develop preventative treatments. The Sun, August 10 2016

Links to Science

Freer R, Sormanni P, Vecchi G, et al. A protein homeostasis signature in healthy brains recapitulates tissue vulnerability to Alzheimer's disease. Science Advances. Published online August 10 2016

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