Investigation into the effects of Alzheimer's drugs on tissue samples from people with Down syndrome: Study raises safety concerns

People with Down syndrome often develop Alzheimer's disease at a young age. Autopsy studies show that the brains of people with Down syndrome have amyloid plaques by age 40. Yet people with Down syndrome have been excluded or underrepresented in clinical trials of new therapies to treat Alzheimer's. Lecanemab, which targets and removes beta-amyloid plaques, has been approved by the U.S. Food and Drug Administration to treat early-stage Alzheimer's disease.

A new study led by researchers at Brigham and Women's Hospital and the University of California, Irvine tested whether lecanemab could bind to amyloid plaques in tissue samples from people with Down syndrome. It found that it was effective at fighting amyloid in all 15 samples. However, the drug also binds to blood vessels in the brain, raising safety concerns. The results were published in JAMA Neurology.

“Our study is highly clinically relevant because we focus on the use of a recently approved disease-modifying therapy for Alzheimer's disease, lecanemab, in people with Down syndrome,” said study co-author Lei Liu, MD, Ph.D., of the Department of Neurology at Brigham and Women's Hospital.

“Our findings underscore the great potential of anti-amyloid drugs to treat people with Down syndrome, but also show that the safety of these drugs needs to be carefully evaluated, particularly the risk of hemorrhagic complications,” said study co-author Dr. Elizabeth Head of the Department of Pathology and Laboratory Medicine at the University of California, Irvine.

The research team examined brain tissue samples from 15 people with Down syndrome between the ages of 43 and 68. The study was limited in its sample size and age range—in the future, researchers hope to expand the study to include samples from younger brain donors to determine whether age might be a factor in how the drug binds to blood vessels.

The team also plans to study the drug's binding profile in people with late-onset Alzheimer's disease to see if it follows a similar pattern. The research team thanks the people with Down syndrome for donating their brains.