A team of scientists, including researchers from University College London (UCL), has discovered key differences in how four Alzheimer’s drugs bind to the toxic amyloid beta protein in the brain.
The findings suggest that lecanemab may be the most effective—especially if given early in the disease.
Published in Alzheimer’s & Dementia, the study was led by researchers at the UK Dementia Research Institute (UK DRI) at UCL, the University of Cambridge, and Belgium’s VIB-KU Leuven Center for Brain & Disease Research.
The researchers tested how well four drugs—lecanemab, donanemab, gantenerumab, and aducanumab—attach to different forms of amyloid beta, the sticky protein that clumps together and is believed to play a central role in Alzheimer’s disease.
Amyloid beta builds up in stages. It starts as small, sticky clumps called oligomers, which then grow into long strands called fibrils, and eventually form larger amyloid plaques in the brain.
These plaques are a hallmark of Alzheimer’s disease.
Scientists still don’t know exactly which stage of the protein buildup does the most damage, but many believe the smaller oligomers may be the most toxic to brain cells.
In the study, the researchers used a new imaging technique to examine how strongly each drug binds to different sizes of amyloid beta aggregates—both in lab models and in real samples from people who died with Alzheimer’s.
The results showed that lecanemab binds best to small, soluble forms of amyloid beta, which are believed to appear early in the disease. It also attaches at more spots along each aggregate, possibly making it more effective at helping the body clear the harmful proteins. This suggests lecanemab could offer the most benefit if given before Alzheimer’s symptoms become severe.
In contrast, aducanumab and gantenerumab were found to bind better to larger aggregates, which form later in the disease. Donanemab didn’t show any binding to the smaller, soluble aggregates—it appears to only target the large, insoluble plaques that collect between brain cells.
The researchers say more studies are needed to determine whether targeting small oligomers or large plaques is more important in slowing or stopping Alzheimer’s.
Professor Bart De Strooper, co-leader of the study, explained that while lecanemab binds well to small toxic forms of amyloid beta, his team also found it attaches effectively to full-blown plaques—much like donanemab. “We still need to understand which target is more important to treat: the small toxic clumps or the larger plaques,” he said.
This study comes as these drugs are under increasing scrutiny and discussion worldwide. Lecanemab and donanemab were approved by the UK’s medicines regulator in 2024, but are not yet available on the NHS, with debates ongoing about their cost and value. In clinical trials, both drugs were shown to slow cognitive decline by about 30%.
Meanwhile, aducanumab was discontinued in 2024 after limited effectiveness, and gantenerumab was dropped in 2022, though it’s now being reworked under a new name: trontinemab.
Co-author Emre Fertan, a PhD student at Cambridge, said the team’s goal was to better understand how these drugs work by identifying which forms of amyloid they target. “Our findings suggest that lecanemab works best against the earliest, most harmful forms of the protein,” he said, “meaning it’s likely to be most effective when used early in the disease.”
The researchers hope this new imaging method can also help in testing future Alzheimer’s drugs and provide insight into how they might work—even before human trials begin. The ability to pinpoint which forms of amyloid beta each drug targets may ultimately lead to better, more personalized treatments for Alzheimer’s disease.
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The research findings can be found in Alzheimer’s & Dementia.
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