A new clinical trial led by Washington University School of Medicine suggests that early intervention with an anti-amyloid drug could delay or even prevent Alzheimer’s-related dementia. The study, published in The Lancet Neurology, focused on individuals with rare genetic mutations that cause early-onset Alzheimer’s disease, providing compelling evidence that removing amyloid plaques from the brain well before symptoms appear may significantly delay cognitive decline.
Key findings: Lowering Alzheimer’s risk by 50%
The study followed 73 participants who inherited genetic mutations that virtually guarantee the development of Alzheimer’s disease in their 30s, 40s, or 50s. Among a subgroup of 22 participants who had no cognitive symptoms at the start and received the experimental drug for an average of eight years, the risk of developing symptoms was cut from nearly 100% to about 50%.
“Everyone in this study was destined to develop Alzheimer’s disease, and some of them haven’t yet,” said senior author Randall J. Bateman, MD, study director and Knight Distinguished Professor of Neurology at WashU Medicine. “We don’t yet know how long they will remain symptom-free—maybe a few years or maybe decades.”
This finding reinforces the amyloid hypothesis, which suggests that the accumulation of amyloid plaques in the brain is the first step toward the condition. By targeting amyloid years before symptoms emerge, researchers hope to slow or halt the progression of the disease.
From mixed results to stronger evidence
Participants were originally part of DIAN-TU-001, the world’s first Alzheimer’s prevention trial. When the trial ended in 2020, researchers reported that gantenerumab, an anti-amyloid drug developed by Roche/Genentech, effectively lowered amyloid levels but had unclear cognitive benefits. To gather more data, trial leaders extended the study, treating all participants with gantenerumab regardless of their previous treatment status.
Although Roche/Genentech halted gantenerumab’s development in 2022 due to disappointing results in a broader trial, the extended study showed that long-term early treatment had a meaningful impact on cognitive decline.
“This study provides the strongest evidence to date that removing amyloid plaques years before symptoms arise can delay the onset of Alzheimer’s,” Bateman explained. “While we still need confirmation from larger studies, these results suggest early intervention could change the course of the disease.”
Next steps: Expanding Alzheimer’s prevention trials
The Knight Family DIAN-TU research team has now launched the DIAN-TU Amyloid Removal Trial to explore the long-term effects of amyloid removal. Since gantenerumab is no longer available, most participants have transitioned to lecanemab, an FDA-approved anti-amyloid drug that slows cognitive decline in symptomatic Alzheimer’s patients.
Maria C. Carrillo, PhD, CSO of the Alzheimer’s Association, emphasized the importance of continued research: “These findings hint at the potential role of lowering beta-amyloid in Alzheimer’s prevention. We look forward to further studies to expand and validate these groundbreaking results.”
In parallel, researchers are enrolling younger participants as early as age 18 in a Primary Prevention Trial to investigate whether stopping amyloid accumulation decades before symptoms appear can prevent the disease altogether.
The future of Alzheimer’s prevention
While this trial focused on genetic early-onset Alzheimer’s, its findings may have broader implications. Both early-onset and late-onset Alzheimer’s follow similar amyloid-driven pathways, meaning future trials could determine whether the same preventive approach could benefit millions at risk for late-onset Alzheimer’s.
“I’m highly optimistic,” Bateman said. “One day soon, we may be able to delay or even prevent Alzheimer’s disease for millions of people.”
