Inside the First International Biobank Studying Down Syndrome and Alzheimer’s

By the time someone with Down syndrome reaches their 50s, there’s a one in three chance they’ll receive a diagnosis of Alzheimer’s disease. By their 60s, that risk jumps to roughly 50%.

Scientists understand the basics of why Down syndrome and Alzheimer’s are linked, but many questions remain, like what the underlying biology is and whether there are any potential treatments. BrightFocus Alzheimer’s Disease Research grant recipient Ann-Charlotte Granholm-Bentley, PhD, DDS, and co-investigators Elliott Mufson, PhD, and Elizabeth Head, PhD, are beginning to answer those questions through an international, collaborative effort to study the brains of people with Down syndrome.

The research will not only shed light on how and why people with Down syndrome develop dementia so young, but also open potential new treatment and prevention avenues for the general population.

Understanding Down Syndrome

Down syndrome is a genetic condition that causes people to have an extra copy of chromosome 21. This chromosome contains a gene that codes for amyloid precursor protein, a molecule that can turn into amyloid plaques, the toxic clumps of protein that clog the brain of people with Alzheimer’s. Because individuals with Down syndrome have more copies of the amyloid precursor protein gene, amyloid may build up faster in their brains. People with Down syndrome are also genetically more prone to inflammation, which can accelerate the development of Alzheimer’s even further.

Together, these factors greatly increase the risk of dementia for people with Down syndrome. Because people with Down syndrome are so likely to develop dementia over time, Alzheimer’s researchers want to better understand the biological changes that underlie dementia development in their brains.

“We know when they are born that they will likely develop Alzheimer’s at a young age, making this group important for studying early signs of disease,” Dr. Granholm-Bentley said. “We can then extrapolate these findings to people with Alzheimer’s in the general population.”

To investigate the biological mechanisms behind Alzheimer’s disease in people with Down syndrome, Granholm-Bentley established the Down Syndrome Biobank Consortium in 2017 with the help of Alzheimer’s Disease Research funding. An international collaboration across multiple research institutions, the first-of-its-kind biobank has now collected over 350 brain donation samples from people with Down syndrome, and about half that in people without Down syndrome to use for comparison. It’s currently the only funded biobank consortium in the United States that concentrates on people with intellectual disabilities.

Researchers at the biobank are studying these brain samples to identify unique molecular changes that happen as people with Down syndrome develop Alzheimer’s disease. The scientists, based both in the U.S. and Europe, are especially interested in the transformations that occur early in the course of dementia. The research could uncover new ways to treat, detect, or prevent dementia in people with Down syndrome, a goal that Dr. Granholm-Bentley says is incredibly important.

“This is a medically underserved group for which there are few medications available when they develop dementia symptoms,” she explained.

Advancing Alzheimer’s Research for Everyone

People with Down syndrome aren’t the only group that stands to benefit from this biobank. Scientists studying these brains could also discover biomarkers or therapeutic targets that apply to the entire population, meaning their research could lead to new ways to detect, treat, or prevent Alzheimer’s for everyone.

Dr. Granholm-Bentley says the support of BrightFocus has been a pivotal resource in founding and maintaining the Down Syndrome Biobank Consortium. Research using donated brain tissue is crucial for understanding human disease, but it’s also expensive and resource-intensive.

“The funding from BrightFocus Foundation came at a time when we had little hope of receiving any support for brain banking of tissue from [Down syndrome],” Dr. Granholm-Bentley said. “We are all so proud of the amount of collaborative spirit that the 11 sites have, and that we have been able to continue despite the harsh funding climate in the USA right now.”

The research could change the lives of the hundreds of thousands of people living with Down syndrome in the U.S., and advance dementia research for everyone, she added.

“The information generated by our project will be of great help to those with Down syndrome and those with Alzheimer’s disease.”

Dr. Granholm-Bentley received follow-on funding to pursue her research in Down Syndrome, including a multi-million dollar federal grant to investigate tau protein as a link between Down Syndrome and Alzheimer’s. Co-investigator Dr. Head now co-leads the Alzheimer’s Biomarkers Consortium – Down Syndrome, a multi-institution research team which was awarded over $100 million in federal funding to expand research on Alzheimer’s biomarkers in adults with Down syndrome.

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