Lecanemab effectively targets amyloid plaques in people with Down syndrome, study finds

People with Down syndrome are likely to develop Alzheimer’s disease at a young age. Autopsy studies show that by age 40, the brains of people with Down syndrome have amyloid plaques. Yet people with Down syndrome are excluded from or underrepresented in clinical trials of new therapies to treat Alzheimer’s. Lecanemab, which has been shown to target and remove beta-amyloid plaques, has been approved by the U.S. Food and Drug Administration to treat AD early in the disease’s progression. A new study led by researchers at Brigham and Women’s Hospital (a founding member of the Mass General Brigham health care system) and the University of California, Irvine, tested lecanemab to see if it could bind to amyloid plaques in tissue samples of people with Down syndrome. that it effectively tackled amyloid in all 15 samples. However, the drug also binds to the blood vessels of the brain, which poses safety risks. Results are published in JAMA Neurology.

Our study is highly clinically relevant as we focus on the use of a recently approved disease-modifying therapy for Alzheimer’s disease, lecanemab, in people with Down syndrome.”

Lei Liu, MD, PhD, co-corresponding author, Department of Neurology, Brigham and Women’s Hospital

“Our findings underscore the exciting promise of anti-amyloid medications for helping people with Down syndrome, but also the need for careful consideration of safety, especially the risk of hemorrhagic complications,” said co-corresponding author Elizabeth Head , PhD, from the Department of Pathology and Laboratory Medicine at the University of California, Irvine.

The research team evaluated brain tissue samples from 15 people with Down syndrome who were between 43 and 68 years old. The study was limited in sample size and age range; In the future, the researchers hope to expand the study to include samples from younger brain donors to determine whether age may be a factor in the drug’s binding to blood vessels. The team also plans to evaluate the drug’s binding profile in people with late-onset AD, to see if it follows a similar pattern. The research team expresses its gratitude to the people with Down syndrome for their gift of brain donation.