Down syndrome research plan revision promotes study of aging

Processes thought to underlie Alzheimer's symptoms in individuals with Down syndrome, others

When opportunity knocks, sometimes he brings along a friend.  At the National Institutes of Health, we hope to help two groups of people—those who have Down syndrome and all others who face Alzheimer’s disease—through research to better understand the development of cognitive impairment with aging.

In fact, this topic and others form the basis of the draft NIH’s Down Syndrome Research Plan (PDF - 771 KB), which is now open for public review and comments. Significant progress has been made on various aspects of Down syndrome research since the NIH Research Plan on Down syndrome was first published in 2007. The plan was revised recently by the Trans-NIH Working Group on Down syndrome, which coordinates research on Down syndrome.  The revised plan includes not only provisions to study the connections between Alzheimer’s disease and Down syndrome, but also other promising areas to improve the health and well-being of those with Down syndrome. People with Down syndrome have an increased risk for a number of health problems, such as cataracts, newborn heart defects, hearing loss, and various auto-immune conditions such as thyroid disease and diabetes.  The NIH institutes collaborate to conduct and support Down syndrome research pertinent to their own individual missions while contributing to the body of knowledge on this condition. 

Last spring, the NIH hosted a meeting, “Advancing Treatments for Alzheimer’s Disease in Individuals with Down Syndrome,” which brought together prominent Down syndrome and Alzheimer’s disease experts to inform the research plan and set the stage for upcoming collaborative projects.

Based on their recommendations, the revised plan now includes provisions for study of the APP gene, which has been linked to both Alzheimer’s disease and Down syndrome. APP contains the instructions for making a protein called amyloid precursor protein.  Researchers are just beginning to understand the protein’s function.  It’s found in many tissues and organs, including the brain and spinal cord.   Beta amyloid, a breakdown product of APP, has been linked to the slow deterioration of memory and thinking skills characteristic of Alzheimer’s disease and also to the high incidence of Alzheimer’s disease seen in Down syndrome.

Estimates vary, but Alzheimer’s disease may affect as many as 5.1 million Americans.  It is the most common cause of dementia—loss of thinking, memory, and reasoning ability.  The dementia begins slowly, but over time often becomes so severe that Alzheimer’s patients must depend on other people to help them with eating, drinking, and other every day activities. 

Alzheimer’s symptoms typically appear later in life—when people are in their 60s and 70s.  For people with Down syndrome, however, Alzheimer’s symptoms often appear much earlier—usually in their mid-50s.  About a third of people with Down syndrome will develop Alzheimer’s dementia in their 50s, and half by their 60s.  Among the general population, about 5 percent of individuals 65-74 have Alzheimer’s disease.

The reason for the increased prevalence and earlier onset of Alzheimer’s appears to be strongly linked to the genetic feature central to Down syndrome.  Down syndrome results from an extra chromosome in the cells of the body.  Instead of having the usual chromosome count of 46, individuals with Down syndrome have 47.  This extra chromosome leads to intellectual disability, distinct facial features, and other hallmarks of the syndrome. 

Specifically, individuals with Down syndrome have an extra copy of chromosome 21.  And it is this chromosome that contains the APP gene.  Under normal conditions, APP is broken down into smaller compounds in the brain.  One of these compounds, beta amyloid, is a key component of amyloid plaques-- the deposits of insoluble protein fragments thought to account for the loss of neurons in the brains of Alzheimer’s patients. For certain rare cases of Alzheimer’s disease in those who do not have Down syndrome, mutations in the APP gene itself appear to account for the Alzheimer’s symptoms.  In Down syndrome, it is the extra copy of the APP gene, and an excess of APP protein, that is thought to be the culprit. However, despite the high prevalence of beta amyloid plaques in the brains of adults with Down syndrome, some people with Down syndrome do not go on to develop Alzheimer’s disease, and it is important to find out why these individuals seem to be protected from the condition.

An objective of the Down Syndrome Research Plan is to capitalize on these insights into APP’s function, to gain an increase understanding of Alzheimer’s in Down syndrome and in others.


The Down syndrome research plan

If you would like to provide comments or feedback on the revised research plan, please see:


If you are a person with Down syndrome or a family member of someone with Down syndrome, you may be interested in DS-Connect®, the new national registry that facilitates information sharing about Down syndrome.  All information provided to the registry is de-identified.  Individuals in the registry can anonymously share their health information with others in the Down syndrome community.  

March Is Trisomy Awareness Month

Down syndrome is the most well-known of many trisomies—conditions resulting from an extra chromosome.  Specifically, Down syndrome results from an extra copy of chromosome 21.  In March, the NICHD joins with other organizations to raise awareness about trisomy conditions and the challenges they can pose to individuals and families.  Effects of having an extra chromosome vary greatly, depending largely on the chromosome that’s involved.  More information about trisomies is available at


Originally posted: March 19, 2014

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