Is there a connection between Alzheimer’s and Down syndrome?

A curious adult from Michigan asks:

"I have heard a lot about Down syndrome and chromosome 21. I have also heard a lot about chromosome 21 and Alzheimer's. Is there any correlation between Alzheimer's and Down syndrome? Isn't chromosome 21 the chromosome that is duplicated when someone has Down syndrome?"

Editor’s note (5/19/2021):At the time this article was written, much less was known about the genetic basis of Alzheimer’s Disease. We now know that there are many other genes besides APP that contribute to Alzheimer’s Disease. You can read more here: Alzheimer’s Disease Genetics Fact Sheet.

You are right, both Alzheimer's and Down syndrome have been linked to chromosome 21. As you probably know, chromosomes have lots of genes, many of which can cause disease when mutated. Chromosome 21, which has around 225 genes, is involved in many diseases.

Alzheimer's and Down syndrome are caused by different changes in chromosome 21. Down syndrome is caused when some or all of chromosome 21 is duplicated. The Alzheimer's link is to a single gene, APP, found on chromosome 21.

Are these two diseases related? Actually, yes they are. People with Down syndrome are much more likely to get Alzheimer’s than the average person.

Alzheimer's disease is a type of mental wear and tear that increases with age. The wear and tear takes the form of memory loss, changes in personality, and a loss of brain function. For example, someone with Alzheimer's disease might not be able to dress themselves even if they are strong enough.

Alzheimer's disease results from changes in the brain that aren't fully understood. These changes are called 'plaques' and 'tangles', which lead to the loss of brain function. Intriguingly, many people with Down syndrome who have lived over the age of 40 develop the same 'plaques' and 'tangles' in their brains.

So what's the connection? Scientists think that it is because of the APP gene, since APP is in a part of chromosome 21 that is absolutely required for Down syndrome. Changes to the APP protein can lead to the harmful brain plaques seen in Alzheimer's disease patients. What's more, mutations in the APP gene have been found in people with a form of Alzheimer's disease that is inherited.

Down syndrome chromosomes.
Down syndrome is caused by an extra copy of chromosome 21. The APP gene, which is linked to Alzheimer’s Disease, is located on chromosome 21.

While it seems likely that the extra copy of the APP gene is responsible for the Alzheimer's seen in Down syndrome, is there any direct evidence? The best evidence comes from mouse models for Down syndrome. These mice have increased levels of APP and their brains look like someone with Alzheimer's.1

Of course, none of this is a smoking gun. While it is likely that people with Down syndrome have increased levels of the APP gene, this has yet to be proven. In addition, it is known that an extra APP gene is not enough to get Alzheimer's — there are more genes on chromosome 21 and other chromosomes involved. So, while we know the genes responsible for Down syndrome, scientists are still trying to understand all the genes implicated in Alzheimer's disease.

So as you can see, the two are related. However, just because diseases happen to share the same chromosome, it doesn't mean that the diseases are necessarily related. For example, even though Fragile X and hemophilia A are both caused by changes to genes on the X chromosome, they aren't really related.


Author: Dr. Colin Davidson

When this answer was published in 2004, Colin was a postdoctoral fellow in the Department of Genetics, studying evolution and function of the Myb gene family in Joseph Lipsick’s laboratory. Colin wrote this answer while participating in the Stanford at The Tech program.

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