PEOPLE with Down syndrome (DS) are genetically predisposed to develop Alzheimer’s disease (AD) neuropathology by age 40 years, making them a critical population for AD-related studies. A recent study has shed light on the binding properties of lecanemab, an anti-β-amyloid immunotherapy, in the brains of individuals with DS.
The study analysed postmortem brain tissue from 15 individuals (53% female) with DS, aged 43–68 years, acquired from AD research centres at the University of California, Irvine, USA, and the University of Kentucky, Lexington, USA from 2008–2021. The researchers focused on the binding patterns of lecanemab, which is becoming increasingly available to people with AD. The aim was to assess how lecanemab interacts with amyloid plaques and brain blood vessels, given the potential inclusion of individuals with DS in future AD clinical trials.
“Our study is highly clinically relevant, as we focus on the usage of a recently approved disease modifying therapy for AD, lecanemab, in people with DS,” said author Lei Liu, Department of Neurology, Brigham and Women’s Hospital, Boston, Massachusetts, USA.
Results showed that lecanemab effectively bound to amyloid plaques in all 15 patients, indicating potential target engagement. However, the study also revealed that lecanemab extensively labelled cerebral amyloid angiopathy (CAA) in brains of individuals with DS. This binding to brain blood vessels raises significant safety concerns.
While lecanemab shows promise in targeting amyloid plaques, the study highlights the necessity for rigorous clinical trials assessing the safety and efficacy of lecanemab in people with DS, particularly those over 43 years old. Close evaluation of CAA-associated amyloid-related imaging abnormalities will be needed. In the future, the team also hopes to include samples from younger brain donors to determine if age is a factor in the drug binding to blood vessels.
Ada Enesco, EMJ
Reference
Liu L et al. Lecanemab and vascular-amyloid deposition in brains of people with down syndrome. JAMA Neurol. 2024; DOI:10.1001/jamaneurol.2024.2579.
