Link Between Down Syndrome and Alzheimer’s Disease Explored

Alzheimer’s disease affects those with Down Syndrome at a far higher rate than the general population.

People with Down syndrome are born with an extra copy of chromosome 21, which carries the APP gene. This gene produces a specific protein called amyloid precursor protein (APP). Too much APP protein leads to a buildup of protein clumps called beta-amyloid plaques in the brain. By age 40, almost all people with Down syndrome have these plaques, along with other protein deposits, called tau tangles, which cause problems with how brain cells function and increase the risk of developing Alzheimer’s dementia.

However, not all people with these brain plaques will develop the symptoms of Alzheimer’s. Estimates suggest that 50 percent or more of people with Down syndrome will develop dementia due to Alzheimer’s disease as they age. People with Down syndrome begin to show symptoms of Alzheimer’s disease in their 50s or 60s.

This spring the Canadian Down Syndrom Resource Center, focused attention on this and on other aging issues facing those with Down Syndrome in both their print publication 3.21 Canada’s Down Syndrom Magazine and on their podcast, The LowDown.

On Episode 3 of The LowDOWN: A Down Syndrome Podcast, Dr. Brian Chicoine, Medical Director of the Adult Down Syndrome Center in Park Ridge, IL, touches on several topics related to optimizing the physical and mental health of adults with Down syndrome.

Guest: Brian Chicoine, MD

Brian Chicoine, MD is the Medical Director of the Adult Down Syndrome Center in Park Ridge, IL.  He is on the faculty of Family Medicine at Advocate Lutheran General Hospital. Dr. Chicoine is co-founder of the Adult Down Syndrome Center which has served and documented the health and psychosocial needs of over 6000 adolescents and adults with Down syndrome since its inception in 1992.  Dr. Chicoine graduated from Loyola University of Chicago Stritch School of Medicine and completed his Family Medicine residency at Lutheran General Hospital. He co-authored two books Mental Wellness of Adults with Down Syndrome and The Guide to Good Health for Teens and Adults with Down Syndrome published by Woodbine House Press. Dr. Chicoine has provided medical care for adults with intellectual disabilities for over 30 years and has presented and written extensively on caring for adults with Down syndrome.

Sections of the Interview with Dr Chicoine Reprinted from

3.21: Canada’s Down Syndrome Magazine

Issue #3: The Health Issue, published Summer 2020

3.21: As adults with Down syndrome move into their forties and beyond, we unfortunately continue to see a high incidence of early onset Alzheimer’s and dementia. What can families do when their loved one with Down syndrome is younger in order to try to prevent this or at least slow down the onset?

Dr. Chicoine: Unfortunately, we still have limited information on that. We know that for people with Down syndrome, as well as the general population, exercise is important in helping either prevent it or slow it down. There is some discussion about whether insulin resistance related to being overweight contributes to Alzheimer’s disease. I don’t think we have a final answer on that yet. But there are lots of good reasons to be physically active, eat healthy and try to stay at a good, healthy weight. If there’s a possible benefit to reducing or preventing Alzheimer’s disease, that’s an added bonus.

There’s a relationship between sleep apnea and Alzheimer’s disease, so certainly we want to make sure people are getting tested for that condition. If you notice that a person’s ability to function or mental health is changing, look at getting a sleep study.

3.21: From time to time, we read exciting reports of research around dementia. Can you tell us what progress is being made in identifying why so many people with Down syndrome develop dementia relatively early and some of the efforts that are being made to address this issue?

Dr. Chicoine: We do see that Alzheimer’s disease does occur at a younger age and more frequently in people with Down syndrome. The APP gene is on chromosome 21, and it is thought that because people with Down syndrome have three copies of chromosome 21, there is more of this gene expression. This seems to contribute earlier and more frequent Alzheimer’s disease. There is a lot of ongoing work looking at what the effect of this gene is, along with other related issues.

As far as potential treatments go, I’m an Edison guy: we’ve had a lot of failed attempts, and we’re really just looking for that one (or more) that works. But ultimately, it probably won’t be just one drug or treatment that brings it under control. I suspect, like a lot of other conditions, that there may be a cocktail of things that we take or do to deal with it.

When I was in medical school, we first started to hear about AIDS and HIV, and at that time it was a terminal illness right from the beginning. Now it is treated very much like a chronic disease, almost like you would treat hypertension or high blood pressure. There is a cocktail of medications and healthy activities that patients can take or do to address it. My hope is that we will see something similar where people with Down syndrome or Alzheimer’s in general may be able to take something and do things to manage it. Or it may be something that can be taken or done at a young age to prevent it from becoming a problem, perhaps in the twenties to forties when the brain is beginning to develop these plaques and tangles. There could be medications that people take at that time to kind of clear that out, if you will.

Some people think that with regards to the ultimate cure for Alzheimer’s, or the control of Alzheimer’s disease, some significant breakthroughs will come through studying people with Down syndrome. Some researchers are studying Alzheimer’s disease in people with Down syndrome for the benefit of the general population, and, to me, that is okay. Ultimately, people with Down syndrome are going to be well served by this.

3.21: Is there a relationship between the buildup of plaques and tangles in the brain and sleep quality?

Dr. Chicoine: This has not yet been definitively proven, but it does seem there may be a link. The chronic oxygen deprivation or low oxygen levels that are seen in people with sleep apnea certainly could be a contributor. Our brains need to have a regular eight-hour sleep cycle with REM sleep and non-REM sleep. And if we don’t have that, our brain does not get the restoration that it needs. Ultimately, good sleep is like healthy eating and exercise: there are many good things that come from good sleep. If it happens to be that it also helps prevent Alzheimer’s, that is an extra plus.

3.21: We can start to see some of these symptoms of early onset Alzheimer’s and dementia in adults with Down syndrome when they are in their thirties and forties, and this population does age at an accelerated rate. Could you explain why these symptoms come on so early for them?

Dr. Chicoine: The onset of symptoms before 40 is actually thought to be fairly uncommon. The youngest person we have diagnosed with Alzheimer’s was 38. The average age of onset of symptoms is about 54, and it is often later than that. But the thing with Alzheimer’s disease is that the changes in the brain start occurring long before the symptoms present themselves. Some studies have found people with Down syndrome, even in their twenties and certainly in their thirties, who already have some of the changes in the brain. That is not unique to Down syndrome; all people can have the changes in the brain long before they actually begin exhibiting the symptoms. But the timeline is shifted to younger ages in people with Down syndrome.

3.21: In recent years, life expectancy for individuals of Down syndrome has increased dramatically. What needs to happen to continue this trend – and not just to help people live longer, but live longer with good health and a good quality of life?

Dr. Chicoine: I had a great uncle that had Down syndrome. He was born in 1907 and he lived to be about 40, which was very unusual in those days. His life expectancy when he was born was only nine. When I graduated from medical school in 1984, life expectancy was about 28. Now it is about 60. That is a dramatic change. If the rest of us had increased by the same percentage, we would all be living to be about 350.

Unfortunately, it does seem to be plateauing around 60 at this point, and Alzheimer’s disease is the big issue that is causing that. So, the next big step is to figure out how can we prevent and treat Alzheimer’s disease successfully. That should have a significant benefit for people with Down syndrome.

3.21: From a parent’s perspective, that’s kind of hard news to hear, because we do not yet have that cocktail of drugs that would help see adults through it. But in terms of what is within the control of individuals with Down syndrome and their families, it sounds like just the regular preventative health measures that all adults, with Down syndrome or not, should be doing: exercising, eating well and sleeping well. Is that really all that families can control?

Dr. Chicoine: I think at this point, those are the things that we know. The other thing I would encourage people to consider is participating in a research study. There are more and more of these studies being done around the world, including Canada. I would consider participating in a study because the more we can learn about this, the better chance we have of preventing and treating it.

For years, I looked at it like, this is a whole chromosome. This is going to be such a such a huge problem to try to fix an entire chromosome. But now researchers have narrowed it down to certain likely genes; maybe it is multiple genes, but it’s no longer the whole chromosome. It is certainly not going to be easy, but we’re getting closer.

Down Syndrome and Alzheimer’s Research

Scientists are working hard to understand why some people with Down syndrome develop dementia while others do not. They want to know how Alzheimer’s disease begins and progresses, so they can develop drugs or other treatments that can stop, delay, or even prevent the disease process.

Research in this area includes:

  • Basic studies to improve our understanding of the genetic and biological causes of brain abnormalities that lead to Alzheimer’s
  • Observational research to measure cognitive changes in people over time
  • Studies of biomarkers (biological signs of disease), brain scans, and other tests that may help diagnose Alzheimer’s—even before symptoms appear—and show brain changes as people with Down syndrome age
  • Clinical trials to test treatments for dementia in adults with Down syndrome

Optimizing Physical and Mental Health 03:38 | 42:54 RewindSpeedForwardInfoShare Chapters The LowDOWN: A Down Syndrome Podcast Optimizing Physical and Mental Health Apr 29, 2020 Season 1 Episode 3 Down Syndrome Resource Foundation

Learn about Alzheimer’s Disease Research Opportunities

For More Information About Down Syndrome and Alzheimer’s

Down Syndrome and Alzheimer’s Disease Resources

Down Syndrome Research and Resources

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