Alzheimer’s progression in Down syndrome appears similar to other early genetic forms of the disease

Press release

Monday, December 12, 2022

An NIH-funded study suggests that people with Down syndrome could benefit from treatments for Alzheimer’s disease.

Amyloid plaques – clumps of protein that are one of the hallmarks of Alzheimer’s disease – occur at about the same level in the brains of people with Down syndrome who have Alzheimer’s disease as in people with Alzheimer’s disease. people with inherited forms of early-onset Alzheimer’s disease, according to research funded by the National Institutes of Health. Based on the largest study of its kind to date, the results suggest that people with Alzheimer’s disease and Down syndrome could benefit from participating in studies of Alzheimer’s disease therapies. aimed at slowing down the formation of amyloid plaques.

The study was led by Beau Ances, MD, Ph.D., of Washington University in St. Louis, and colleagues from the Predominantly Inherited Alzheimer’s Network (DIAN) and the Alzheimer’s Biomarkers Consortium – Down Syndrome (ABC-DS). He appears in Lancet Neurology. NIH funding was provided by the National Institute on Aging (NIA), the Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD) and the Lifetime Comorbidity Survey Project to Understand Down Syndrome.

“The similarity suggests that there may be common mechanisms underlying Alzheimer’s disease in people with Down syndrome and other inherited forms of Alzheimer’s disease,” said Diana W. Bianchi , MD, Director of NICHD. “Future advances in understanding Alzheimer’s disease in people with Down syndrome may contribute to a better understanding of other forms of the disease.”

Plaques are composed largely of aggregated beta-amyloid proteins, which are encoded by the amyloid precursor protein (APPLICATION) and is found on chromosome 21. Because people with Down syndrome are born with an extra full or partial copy of chromosome 21, they have three copies of APPLICATION embarrassed. This causes them to produce too much amyloid-beta protein, leading to plaque formation.

For the current study, the researchers periodically performed MRIs and amyloid positron emission tomograms of the brains of people with Down syndrome. They then compared the results to brain scans of people with early-stage Alzheimer’s disease resulting from the inheritance of disease-causing variants of the APPLICATION gene or the DOG1 Where PSEN2 genes, which code for enzymes that break down amyloid precursor proteins.

The study involved 192 people with Down syndrome and 33 sibling controls from the ABC-DS trial. It also involved 265 transporters from APPLICATION, DOG1Where PSEN2 variants and 169 non-carrier family members who participated in the NIA-funded DIAN trial, also being part of the control group.

“Multiple pathways may mediate brain damage in Alzheimer’s disease and related dementias,” said Richard J. Hodes, MD, director of the NIA. “Studies like this can help researchers understand commonalities or differences in the pathways that mediate brain damage in distinct at-risk populations, such as those with Down syndrome and those with Down syndrome. Early-onset and dominantly hereditary Alzheimer’s disease. These findings may thus provide clues for developing treatments for these devastating disorders.

Overall, the amount of amyloid load was similar in the brains of people with Down syndrome to those who carry the genetic variants of early forms of Alzheimer’s disease. For both groups, amyloid levels in the brain were higher than in the control group. Additionally, participants with Down syndrome and early Alzheimer’s disease who showed signs of cognitive decline on thinking and memory tests had higher levels of amyloid than their counterparts who showed no signs of cognitive decline. cognitive decline.

A difference between the two groups was observed in the pattern of cerebral amyloid plaque formation. Participants who had early onset Alzheimer’s disease had plaques in all areas of the Cerebral cortex, the outermost layer of the brain. In contrast, the brains of people with Down syndrome had no plaque deposits in the middle of the occipital lobe, the part of the cerebral cortex at the back of the brain.

The authors concluded that people with Down syndrome may show a pattern of amyloid accumulation in the brain very similar to that seen in people with early forms of Alzheimer’s disease. The results also show the benefit of including people with Down syndrome in clinical trials – health advances are being made for people with Down syndrome as well as the general public.

About Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD): NICHD conducts research and education to understand human development, improve reproductive health, improve the lives of children and adolescents, and maximize the capabilities of all. For more information, visit

About the National Institute on Aging (NIA): The NIA leads the US federal government’s efforts to conduct and support research on aging and the health and well-being of older adults. Learn about age-related cognitive changes and neurodegenerative diseases via NIAs Alzheimer’s Disease and Related Dementias Education and Guidance Center (ADEAR) website. Visit the main NIA website for information on a range of aging-related topics, including English and Spanishand Stay logged in.

About the National Institutes of Health (NIH):The NIH, the country’s medical research agency, comprises 27 institutes and centers and is part of the US Department of Health and Human Services. The NIH is the primary federal agency that conducts and supports basic, clinical, and translational medical research, and studies the causes, treatments, and cures for common and rare diseases. For more information about the NIH and its programs, visit

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Boerwinkle AH, et al. Comparison of amyloid load in people with Down syndrome versus autosomal dominant Alzheimer’s disease: a cross-sectional study. The Lancet Neurology (2022).


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