In people with Alzheimer’s dementia, amyloid beta proteins accumulate in the brain and form plaques. Antibody therapies aim to remove these clumped proteins. Two such active ingredients have been available in Germany since autumn 2025. But now a large overview study shows that such anti-amyloid therapies have no clinical benefit for those affected, but do increase the risk of swelling and microbleeds in the brain.
The neurodegenerative disease Alzheimer’s is the most common cause of dementia. This causes plaques made of amyloid beta proteins to build up in the brain and the nerve cells gradually die off. As the disease progresses, those affected increasingly lose their cognitive abilities and are ultimately no longer able to cope with everyday life on their own. There is currently no cure for Alzheimer’s disease.
A new treatment approach involves removing the amyloid beta plaques from the brain at an early stage of the disease using special antibodies. The hope was to slow down cognitive decline so that those affected would remain independent for longer. The two active ingredients lecanemab and donanemab have been available in Germany since autumn 2025 and, according to studies, can reduce plaques in the brain. But do these therapies actually ensure that mental decline progresses more slowly?
Statistically significant but not clinically relevant
To clarify this question, a team led by Francesco Nonino from the Institute of Neuroscience in Bologna evaluated data from 17 clinical studies with a total of 20,342 participants for a meta-analysis as part of the Cochrane research network. All included studies had examined people in the early stages of Alzheimer’s who had received either anti-amyloid antibodies or a placebo drug.
“Unfortunately, the evidence suggests that these medications do not make a meaningful difference for patients,” says Nonino. Although the antibodies are actually able to remove amyloid plaques from the brain, cognitive decline progresses almost unabated – regardless of whether a person was treated with antibodies or a placebo. “After 18 months of treatment, anti-amyloid monoclonal antibodies likely have little to no effect on the decline in memory and thinking skills or on the ability to carry out everyday activities,” the researchers report.
According to the studies evaluated, antibody preparations could possibly bring about a slight improvement in more complex everyday tasks such as financial management and taking medication. But this is probably so small that it hardly makes a difference for patients in practice. “While early studies showed statistically significant results, it is important to distinguish between statistically significant and clinical relevance,” explains Nonino. “It is common for studies to produce statistically significant results but do not translate into a meaningful clinical difference for patients.”
Hardly any effect, but side effects
In addition, the overview study shows that the anti-amyloid drugs hardly have any desired effects, but they do have detectable side effects. 119 out of 1,000 people who received antibody therapy developed brain swelling, while this symptom only occurred in 12 out of 1,000 people in the placebo group. Microbleeds in the brain also increased slightly in the treatment group. These side effects are usually not associated with serious consequences, but often only show up in a brain scan. In some cases, however, headaches, dizziness, nausea or other complications occur. The researchers did not find a difference in mortality.
At the time of the evaluation, six studies on the effect of anti-amyloid antibodies had not yet been completed. “The conclusions of this review may change as new results become available,” write Nonino and his team.
Co-author Edo Richard from the Radboud University Medical Center in the Netherlands regularly treats people with Alzheimer’s. “I wish I had an effective treatment to offer them,” he says. “Although existing approved medications provide some benefit to some patients, there remains a large unmet need for more effective treatments. Unfortunately, anti-amyloid medications do not provide this and pose additional risks. Given the lack of association between amyloid removal and clinical benefit, we must explore other avenues to combat this devastating disease.”
Source: Francesco Nonino (IRCCS Istituto delle Scienze Neurologiche di Bologna, Italy) et al., Cochrane Database of Systematic Reviews, doi: 10.1002/14651858.CD016297