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Health & Wellness

What 42 previously unknown genes may tell us about treating Alzheimer’s disease

Alzheimer's,Disease,On,Mri
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A medical professional examines Alzheimer's Disease on an MRI

The genes were discovered in what has been described as the largest study of genetic risk for the disease to date.
Dr. Diana Kerwin, a geriatric medicine specialist with Texas Health Dallas, talked with KERA’s Sam Baker about the potential for this new information.

Importance of the discovery

What we can do is look at what does that gene code for? What is it associated with? And that can help us find the pathways that lead to the disease. And then you start to work backward from there. How can we start to develop medications that target that particular pathway to stop that process from occurring?

So knowing these genetic risk markers or risk factors that we hadn't known before really helps to open up more therapeutic development and just by increasing our understanding of why Alzheimer's pathology forms in some people and not others.

For instance, some of the newly discovered genes may make our immune system less efficient?

One of the main areas was the immune system, and also some scavenger cells are clean-up cells in the brain called microglia. And there were some genes that were identified that were associated with decreased function of those microglia. So they're not cleaning up the toxic protein species in the brain as they should.

And so you can imagine that if you can then start to focus on that risk factor in that gene, can you start to reverse that so the microglia and those clean-up cells can continue to function at a normal level so that you might be able to prevent those toxic protein species from accumulating in the brain, which we know is what leads to the dementia syndrome many years down the road.

Another key pathway involves genes associated with inflammation.

And that may actually help us explain why some people, even if they only have mild hypertension, seem to develop Alzheimer's at a much faster pace.

It may help us to identify for individuals why the interaction of their genes, and maybe their slightly elevated blood pressure or their slightly elevated cholesterol, seems to have a compound effect. Whereas in other individuals, it may not have as much of a pronounced effect.

It does go back to the underlying advice we have for patients as far as paying attention to your own cardiovascular risk factors. That's why we say exercise and diet to reduce inflammation.

One of the insights of the study was that brain disorders such as Parkinson's or Lewy body disease and ALS may have the same underlying genetic basis. Why is that important to know?

There are actually maybe more similarities between them than we thought. Often, a lot of research is focused on Alzheimer's, but what it tells us is that a finding in Alzheimer's research or finding and frontotemporal dementia research can actually help us find new therapies for potentially several of the dementia syndromes.

That was a really important finding because I think it helps us take a bit of a broader scope at looking at these risk factors and saying this patient may be at risk not only for Alzheimer's but for other general disorders because this particular gene is present.

We know lifestyle choices like smoking and diet and exercise can influence Alzheimer's development. But from everything you're saying, and from the study, the much-needed answers everyone is looking for really lie in genetics.

We do know that the genetic background is very important to understand, but we don't want to just leave it there and say, Well, if it's in your genetic risk factor, you can't do anything about it.

The knowledge of the genetic makeup and genetic risk factors will help us inform individual precision medicine. What's your genetic risk background? And then what are the lifestyle at risk mitigators that we could introduce to try to offset those genetic risk markers?

I think although we all want to know if it's in our genes, we don't want to be passive about it because that actually can help us to inform, even more importantly and emphasize the importance of taking control of your risk factors and trying to reduce them so that you, as an individual can reduce your risk of developing Alzheimer's.

RESOURCES:

Alzheimer’s study

42 previously unknown genes discovered for Alzheimer's disease

What is Alzheimer’s Disease?

Interview highlights were lightly edited for clarity.

Got a tip? Email Sam Baker at sbaker@kera.org. You can follow Sam on Twitter @srbkera.

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