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A multi-institution research team led by the University of Pittsburgh School of Medicine has been awarded a five-year grant to total $109 million from the National Institutes of Health (NIH). The funding, which will expand research on the biomarkers of Alzheimer’s disease in adults with Down syndrome, is the largest grant to ever be awarded to the University of Pittsburgh Department of Psychiatry.
The Department is the lead site for the Alzheimer’s Biomarkers Consortium – Down Syndrome (ABC-DS), which involves nine Pitt departments and 16 external collaborating sites.
Funding support for this award is provided by NIH’s National Institute on Aging, the Eunice Kennedy Shriver National Institute of Child Health and Human Development and the INCLUDE (INvestigation of Co-occurring conditions across the Lifespan to Understand Down syndromE) project. The INCLUDE project seeks to investigate conditions that affect individuals with Down syndrome and the general population, such as Alzheimer’s disease, autism, cataracts, celiac disease, congenital heart disease and diabetes.
“This historic grant is a direct reflection of the world-class physicians who call the University of Pittsburgh’s Department of Psychiatry home,” said Anantha Shekhar, MD, PhD, senior vice chancellor for the health sciences. “I look forward to seeing their talents in action—and the University’s mission of creating and leveraging knowledge for society’s gain in full swing—in the years to come.”
“Adults with Down syndrome are at high risk for developing Alzheimer’s disease because of their unique biology, usually starting in their late 40s, and the vast majority of individuals with Down syndrome will eventually develop the disease by their late 60s,” said principal investigator Benjamin Handen, PhD, professor of psychiatry at Pitt. “It’s a significant problem for that population. We think that what we learn from the biomarkers in people with Down syndrome can help them, and also the general population in terms of how we can intervene. We’re hoping this research will guide us toward prevention and treatment trials.”
“The increased deposition of amyloid in the brain is thought to be the initiating step for developing Alzheimer’s disease in many individuals. Adults with Down syndrome overproduce amyloid, due to the presence of three copies of chromosome 21, each containing a copy of the Amyloid Precursor Protein gene, similar to those with autosomal dominant mutations that cause Alzheimer’s disease, said Dr. Handen. “Dr. William Klunk and his colleagues developed Pittsburgh Compound B, a PET radiotracer, almost two decades ago, which allows us to measure amyloid deposition in the living brain. They approached us, given our ongoing work with individuals with Down syndrome, and we were able to recruit a group of adults with Down syndrome who underwent PET scans with Pittsburgh Compound B—laying the groundwork for the current study.”
The ABC-DS research team will follow a cohort of people with Down syndrome to conduct three projects focused on the following lines of investigation:
“It’s very exciting that the National Institutes of Health is investing in the science and infrastructure to strengthen our relationship with the Down syndrome community,” said Ann D. Cohen, PhD, associate professor of psychiatry at Pitt who is leading outreach efforts in this study through the Alzheimer's Biomarkers Consortium — Down Syndrome Outreach, Recruitment and Education Core. “Things like developing novel recruitment strategies and increasing efforts to connect with a diverse population of people with Down syndrome will contribute to better science and help researchers understand what the Down syndrome community needs from us.”
The research teams will assess and examine a wide range of data from plasma-based biomarkers to biofluids, genetic factors, neuroimaging and everyday cognitive and psychological function. Researchers will see participants every 16 months for up to four visits.
This research will be funded by NIH grant U19AG068054.