What Can Down Syndrome Tell Us About Alzheimer’s Disease and Aging?

Aurélie Ledreux, PhD & Lotta Granholm-Bentley, PhD/DDS

Department of Neurosurgery at the University of Colorado Anschutz Medical Campus

  • Research News
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Dr. Granholm-Bentley received a 2017-23 Alzheimer’s Disease Research grant from BrightFocus to create the International Brain Bank for Down Syndrome-Related Alzheimer’s Disease, a collaborative research network focused on developing and sharing high-quality biological research samples and studying much-needed information about the Down syndrome population. Up to 80 percent of all Down syndrome individuals develop Alzheimer’s by the time they are in their 50s and 60s, and the project is exploring the neurobiological mechanisms underlying the onset of Alzheimer's disease-type dementia in Down syndrome, as well as possible treatment targets for this population. Co-principal investigators on the grant include Elizabeth Head, PhD, of The University of California, Irvine; and Elliott Mufson, PhD, of the Barrow Neurological Institute.

Aging with Down syndrome

Down syndrome (DS) is the most common survivable genetic syndrome and is caused by having three instead of two copies of the whole or part of Chromosome 21. Children who are born with DS (about 1 in 700 births in the US) have a characteristic appearance with a flattened curvature of the face, outside corners of the eyes that point upward, small ears, a short neck, and a large tongue. They experience delayed development of learning and memory and movement function, but not all areas of cognition are equally affected. For example, children with DS have well developed social skills, smiling, and communicating non-verbally early. As they grow older, they may have difficulties in motor and verbal learning, but are stronger in visual cues – suggesting that using visual tools during learning of a task can improve their functionality. Over the last decades, medical advances and earlier diagnosis of diseases have made it possible for individuals with DS to live much longer – they would only live into their teens in the 70s but now have an average life span of 58-60 years of age.

What happens in the brain with aging?

Activated inflammatory cells plaque in AD
Figure 1. A= Activated inflammatory cells. B = Plaque in AD brain consisting of the protein amyloid-beta (blue), a toxic protein contributing to pathology. C = Tangles (arrows) in DS and AD in neurons resemble “flames” that will kill the nerve cell.

With the incredible increase in life span in those with DS comes exposure to age-related conditions. These include dementia, visual and hearing impairment, epilepsy, and thyroid disorders. Further, Chromosome 21 harbors several genes that scientists believe are implicated with Alzheimer’s disease (AD). Because individuals with DS have an extra copy of chromosome 21, most of them develop AD pathology in their brain by their third or fourth decade and dementia symptoms in the 40s-60s. Researchers have identified several processes in the brain that could be responsible for the high incidence of AD in DS. First, those with DS have a heightened immune response and inflammation plays an important role in the brain pathology of AD (Figure 1). Second, there are proteins that are important for normal brain function but for some reason are clumping up into aggregates called “plaques” and “tangles” (see Figure 1). When these proteins become dysfunctional, nerve cells die, and inflammation is ramped up. Finally, a phenomenon called “oxidative stress” is responsible for putting stress on nerve cells and other cells in the brain, contributing to the loss of cells and propagating the pathology.

What can families do to help someone with DS and AD? 

Dementia is difficult to diagnose in those with DS, since they already may have varying degrees of intellectual disabilities or hearing or vision loss. A physician who specializes in intellectual disabilities may better understand how to test whether someone has dementia symptoms. Resources, support groups, and education have recently become available for families for example via the National Institutes of Health Down syndrome Resource page (1) and the National Down syndrome Society (https://www.ndss.org).  Dementia associated with DS requires specialist care and a better understanding of biological mechanisms involved, but persons with DS often do not get the help they need since there is a lack of resources for clinical treatment of dementia in DS. Other age-related conditions may affect performance on learning and memory tasks. For example, a vision or hearing loss affects someone’s ability to understand and do the tasks. Sleep apnea – which is extremely common in those with DS – can highly affect someone’s ability to perform well on these tasks as well. Therefore, finding out if someone has these other conditions can help distinguish them from true dementia.  

Families often ask if there are lifestyle changes that can help slow the progression of dementia in those with DS and AD. We know a lot more about lifestyle and dementia in the general population, but recent studies have suggested that moderate amounts of exercise (such as walking or using a treadmill) can slow the progression of dementia also in DS. Persons with DS are often overweight in their middle-age and obesity has been connected strongly with inflammation and oxidative stress in the brain, although not proven specifically for DS. Finally, there are diets that affect dementia and AD pathology in the brain. So-called “anti-oxidant” diets (that will stave off the oxidative stress mentioned above) include salmon, green leafy vegetables, blueberries, acai, and dragon fruit. Ingredients found in green tea have been tested in a population of older adults with DS and had some effects on memory function. In general, it is safe to say that healthy habits that have proven effective on dementia prevention in the general population will also benefit those with DS, although research is still being conducted.

Brain donation and how this can help 

The Down syndrome biobank consortium (DSBC) is a 10-site biobank focused on collecting and studying tissues from persons with DS of all ages. Examining the brain is important because only then can researchers fully understand what goes on in terms of pathological processes, and how the brain of someone with DS and AD differs from AD in the general population. This will allow development of new treatment paradigms and will be very important for effective help to patients. Across many states in the US and in Europe, researchers are working on better understanding biological processes involved in AD and in DS-AD. To date, this is the only way to fully investigate what a person died from and how this could have been prevented. The DSBC consortium is funded by Bright Focus. If you are interested in finding out more about this network of researchers, and how you can help, please visit our website below (2).

Summary 

To conclude, persons with DS have a longer life span than ever before, and therefore are subject to age-related conditions including Alzheimer’s disease dementia. Diagnosis of dementia can be difficult unless a specialist on intellectual disabilities is available but there are more resources than ever before for families and physicians. Life-style factors definitely play a role to reduce or accelerate pathology in the brain and it is important to get a baseline examination of memory and learning function before someone declines into dementia symptoms. There are new medications that are being tested for persons with DS and AD, but these are currently under investigation and may be available soon.

Resources 

  1. https://www.nichd.nih.gov/health/topics/down/resources/patients

  2. https://devdownsbio.wpengine.com/

About the Authors

ledreux headshot

Dr. Aurélie Ledreux, PhD

Dr. Ledreux is an Assistant Professor in the Department of Neurosurgery at the University of Colorado Anschutz Medical Campus. Her current research focuses on developing biomarkers for Alzheimer’s disease, Down syndrome, and sports-related traumatic brain injury.

grantholm bentely headshot

Dr. Lotta Granholm-Bentley, PhD/DDS

Dr. Granholm-Bentley is a Professor in the Department of Neurosurgery at the University of Colorado Anschutz Medical Campus. She is originally from Sweden and has been working in the aging field for more than 35 years. Her work is focused on neurodegenerative diseases in terms of early diagnosis and novel treatments.


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