Studying Alzheimer’s biomarkers in Down syndrome
Larry H. Bernstein, MD, FCAP, Curator
LPBI
NIH supports new studies to find Alzheimer’s biomarkers in Down syndrome
Groundbreaking initiative will track dementia onset, progress in Down syndrome volunteers
The National Institutes of Health has launched a new initiative to identify biomarkers and track the progression of Alzheimer’s in people with Down syndrome. Many people with Down syndrome have Alzheimer’s-related brain changes in their 30s that can lead to dementia in their 50s and 60s. Little is known about how the disease progresses in this vulnerable group. The NIH Biomarkers of Alzheimer’s Disease in Adults with Down Syndrome Initiative will support teams of researchers using brain imaging, as well as fluid and tissue biomarkers in research that may one day lead to effective interventions for all people with dementia.
The studies will be funded by the National Institute on Aging (NIA) and the Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD), both part of NIH. The institutes are jointly providing an estimated $37 million over five years to two highly collaborative projects, which enlist a number of leading researchers to the effort. To advance Alzheimer’s research worldwide, the teams will make their data and samples freely available to qualified researchers.
“This is the first large-scale Alzheimer’s biomarker endeavor to focus on this high-risk group,” said Laurie Ryan, Ph.D., chief of the Dementias of Aging Branch in NIA’s Division of Neuroscience, which leads NIH research on Alzheimer’s. “Much like the long-established Alzheimer’s Disease Neuroimaging Initiative, the goal of this initiative is to develop biomarker measures that signal the onset and progression of Alzheimer’s in people with Down syndrome. Hopefully, one day, we will also use these biomarkers to determine the effectiveness of promising treatments.”
The link between Alzheimer’s and Down syndrome is well-known. People with Down syndrome are born with an extra copy of chromosome 21, which contains the amyloid precursor protein gene. This gene plays a role in the production of harmful amyloid plaque, sticky clumps that build up outside neurons in Alzheimer’s disease. Having three copies of this gene is a known risk factor for early-onset Alzheimer’s that can occur in people in their 30s, 40s and 50s. By middle age, most but not all adults with Down syndrome develop signs of Alzheimer’s, and a high percentage go on to develop symptoms of dementia as they age into their 70s.
The initiative establishes funding for two research teams that will pool data and standardize procedures, increase sample size, and collectively analyze data that will be made widely available to the research community. The teams will employ an array of biomarkers to identify and track Alzheimer’s-related changes in the brain and cognition for over 500 Down syndrome volunteers, aged 25 and older. The measures include:
- Positron emission tomography (PET) scans that track levels of amyloid and glucose (energy used by brain cells); MRI of brain volume and function; and levels of amyloid and tau in cerebrospinal fluid and blood;
- Blood tests to identify biomarkers in blood, including proteins, lipids and markers of inflammation;
- Blood tests to collect DNA for genome-wide association studies that identify the genetic factors that may confer risk, or protect against, developing Alzheimer’s;
- Evaluations of medical conditions and cognitive and memory tests to determine levels of function and monitor any changes;
- For the first time in people with Down syndrome, PET brain scans that detect levels of tau, the twisted knots of protein within brain cells that are a hallmark Alzheimer’s disease.
Aside from earlier onset, Alzheimer’s in people with Down syndrome is similar to Alzheimer’s in others. The first symptom may be memory loss, although people with Down syndrome initially tend to show behavior changes and problems with walking.
“Over the past 30 years, the average lifespan of people with Down syndrome has doubled to 60 years—a bittersweet achievement when faced with the possibility of developing Alzheimer’s,” said Melissa Parisi, M.D., Ph.D., chief of the NICHD Intellectual and Developmental Disabilities Branch, which leads NIH’s Down syndrome research. “There is much to learn about Alzheimer’s in Down syndrome, and we’re hopeful that these new projects will provide some answers. One mystery we hope to solve is whether or not the disease progresses at a faster rate in this group.”
Parisi noted that research into Alzheimer’s in Down syndrome is a key focus of the National Plan to Address Alzheimer’s Disease(link is external), which calls for improved care for specific populations that are unequally burdened by the disease, including people with Down syndrome, and for increased research that may lead to possible Alzheimer’s therapies.
Benjamin Handen, Ph.D., Department of Psychiatry, University of Pittsburgh, heads a team that involves investigators and data from: Banner Alzheimer’s Institute, Phoenix; Cambridge University, England; Alzheimer’s Disease Cooperative Study, San Diego; Laboratory of Neuro Imaging, University of Southern California, Los Angeles. Nicole Schupf, Ph.D., Columbia University Medical Center, New York City, leads a team involving investigators at: University of California, Irvine; Kennedy Krieger Institute/Johns Hopkins University, Baltimore; Massachusetts General Hospital/Harvard University, Boston; and the University of North Texas Health Sciences Center, Fort Worth.
Learn more about this topic at https://www.nia.nih.gov/alzheimers/publication/alzheimers-disease-people-down-syndrome.
About the Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD): The NICHD sponsors research on development, before and after birth; maternal, child, and family health; reproductive biology and population issues; and medical rehabilitation. For more information, visit the Institute’s website at http://www.nichd.nih.gov.
About the National Institute on Aging: The NIA leads the federal government effort conducting and supporting research on aging and the health and well-being of older people. It provides information on age-related cognitive change and neurodegenerative disease specifically at its Alzheimer’s Disease Education and Referral (ADEAR) Center at www.nia.nih.gov/alzheimers.
About the National Institutes of Health (NIH): NIH, the nation’s medical research agency, includes 27 Institutes and Centers and is a component of the U.S. Department of Health and Human Services. NIH is the primary federal agency conducting and supporting basic, clinical, and translational medical research, and is investigating the causes, treatments, and cures for both common and rare diseases. For more information about NIH and its programs, visit www.nih.gov.
NATIONAL PLAN TO ADDRESS ALZHEIMER’S DISEASE: 2015 UPDATE
pdf-document/national-plan-address-alzheimer%E2%80%99s-disease-2015-update (58 PDF pages)
Vision Statement
National Alzheimer’s Project Act
Alzheimer’s Disease and Related Dementias
The Challenges
Framework and Guiding Principles
Goals as Building Blocks for Transformation
2015 Update
The Connection between Down Syndrome and Alzheimer’s Disease
Many, but not all, people with Down syndrome develop Alzheimer’s disease when they get older. Alzheimer’s is an irreversible, progressive brain disorder that slowly destroys memory and thinking skills and, eventually, the ability to carry out simple tasks.
Alzheimer’s disease is the most common cause of dementia among older adults. Dementia is the loss of cognitive functioning—thinking, remembering, and reasoning—and behavioral abilities to such an extent that it interferes with a person’s daily life and activities.
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 into their 70s.
Alzheimer’s Disease Symptoms
Many people with Down syndrome begin to show symptoms of Alzheimer’s disease in their 50s or 60s. But, like in all people with Alzheimer’s, changes in the brain that lead to these symptoms are thought to begin at least 10 years earlier. These brain changes include the buildup of plaques and tangles, the loss of connections between nerve cells, the death of nerve cells, and the shrinking of brain tissue (called atrophy).
The risk for Alzheimer’s disease increases with age, so it’s important to watch for certain changes in behavior, such as:
- increased confusion
- short-term memory problems (for example, asking the same questions over and over)
- reduction in or loss of ability to do everyday activities
Other possible symptoms of Alzheimer’s dementia are:
- seizures that begin in adulthood
- problems with coordination and walking
- reduced ability to pay attention
- behavior and personality changes, such as wandering and being less social
- decreased fine motor control
- difficulty finding one’s way around familiar areas
Currently, Alzheimer’s disease has no cure, and no medications have been approved to treat Alzheimer’s in people with Down syndrome.
Down Syndrome and Alzheimer’s Disease Research
Alzheimer’s can last several years, and symptoms usually get worse over time. 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. Clinical trials are best the way to find out if a treatment is safe and effective in people.
Alzheimers Disease Neuroimaging Initiative (ADNI)
A public-private partnership, the purpose of ADNI is to develop a multisite, longitudinal, prospective, naturalistic study of normal cognitive aging, mild cognitive impairment (MCI), and early Alzheimer’s disease as a public domain research resource to facilitate the scientific evaluation of neuroimaging and other biomarkers for the onset and progression of MCI and Alzheimer’s disease.
Dr. Laurie Ryan of the NIA gives a brief overview of ADNI in this video:
Dr. Thomas Obisesan of Howard University, an ADNI study participant, and a study companion describe ADNI and what it’s like to be involved in the study
Learn more about this topic at https://www.nia.nih.gov/alzheimers/publication/alzheimers-disease-people-down-syndrome.
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