Blood Proteins Show Promise as Monitors for Alzheimer Treatment Response

A straightforward blood test could one day provide doctors and patients with an indication of whether an Alzheimer’s therapy is having an effect. A recent investigation at Washington University School of Medicine in St. Louis located dozens of blood plasma proteins that can be visibly affected during the administration of the anti-amyloid treatment lecanemab, marketed as Leqembi. The results, published in The Lancet Neurology September 24 2023 pave the way for less expensive methods of monitoring therapeutic response beyond brain imaging.

This clinical trial was conducted on close to 200 patients with early symptoms of Alzheimer who received therapy of lecanemab infusions every two weeks for 2 years. Blood samples were taken at various times throughout the duration of therapy and were compared to levels in cognitively healthy individuals. It was observed that there were 34 proteins that had changed a lot. Many of these biomarkers were corrected to range within those expected of someone without the disease, indicating that the drug was aiding in the removal of the dangerous buildup of amyloids in the brain.

Until now, clinicians have had few alternatives to assess the success of anti-amyloid drugs in a patient. While the decreasing plaques can be viewed by brain imaging, scans are costly and not readily accessible or practical for repeated assessments. Cognitive tests provide another measure, but can vary for reasons other than the drug itself. The finding of the blood proteins gives potential compromise. Some show a strong correlation with amyloid clearance, while others seem to have a relationship with cognitive changes. Collectively they provide another piece of the puzzle.

Best co-senior author, Suzanne Schindler, professor of neurology at WashU Medicine, reflected the real-life problem: ‘patients always want to know directly if the drug is helping them. If you don’t have a precise marker like this, it’s very hard to definitively answer that question. The new protein signatures could go a long way towards providing that information in the future.’

Another senior author and director of the NeuroGenomics and Informatics Center at the university, Carlos Cruchaga, observed that many Alzheimer’s-related markers had moved in a favorable direction. This indicates the treatment isn’t just clearing out plaques but also affecting processes in general that can be detected in the blood. The team of researchers was careful to point out that the results were early and quite preliminary. Larger trials will be needed to identify the proteins that are best markers and how they should be used in everyday clinical practice.

When we discover it impacts the treatment. Anti-amyloid drugs like lecanemab are some of the first options for disease-modifying treatments. They won’t work for every patient, and we will need better understanding of the risks involved, but having a drug we can measure response to more easily would be extremely useful to determine if we keep going down that road, change direction or turn anywhere else. It will also potentially cut down on repeated imaging and associated cost and effort (patient, health care).