Blood proteins shift during Alzheimer's treatment and may help monitor the effects of the medication

by Shawn Ballard, Washington University in St. Louis

edited by Sadie Harley, reviewed by Robert Egan

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Patients with early symptoms of Alzheimer's disease may be prescribed anti-amyloid therapy, which can help clear the sticky clumps of amyloid protein in the brain that characterize Alzheimer's. While these treatments cannot cure Alzheimer's or restore cognitive function to normal, they have been shown to slow the progression of the disease. Their effects may vary, and clinicians have had no way to monitor treatment in an individual patient besides expensive brain scans.

A new study from Washington University School of Medicine in St. Louis of nearly 200 patients receiving lecanemab, an anti-amyloid treatment marketed under the brand name Leqembi, identified dozens of blood proteins that change during treatment. Levels of these proteins, or biomarkers, reflect brain health, and the study identified which ones could potentially help monitor treatment effects.

The results appear in The Lancet Neurology.

"When patients want to know how the anti-amyloid treatments are working, it's difficult to provide a clear answer," said co-senior author Suzanne Schindler, M.D., Ph.D., a professor of neurology at WashU Medicine.

"We know from clinical trials that anti-amyloid treatments are likely to help the average patient with early symptoms of Alzheimer's, but right now we have limited tools to monitor treatment effects. It would be very helpful to have a blood test that told us how the treatment was working in an individual patient, especially whether amyloid is being cleared from the brain and how the brain is changing."

What can blood proteins reveal about Alzheimer's treatment?

The study by Schindler and co-senior author Carlos Cruchaga, Ph.D., the Barbara Burton and Reuben M. Morriss III Professor in the Department of Psychiatry, included 197 patients with symptoms of early Alzheimer's disease and evidence of amyloid buildup who received lecanemab infusions every two weeks for up to two years.

All the patients were treated at WashU Medicine's Memory Diagnostic Center, which runs one of the highest-volume anti-amyloid treatment clinics in the country. They provided blood samples roughly every six months and underwent cognitive testing. A subset of patients underwent brain imaging as well.

The research team was led by Rui Mu, a graduate student in Cruchaga's lab, who measured 130 proteins in plasma, the liquid portion of the blood. The team tracked how protein levels shifted with treatment and looked for relationships between protein levels, changes in patients' cognitive scores and amyloid clearance shown on brain scans.

Patients treated with lecanemab were compared with 458 people with no cognitive impairment or amyloid buildup and 1,312 people from WashU Medicine's Knight Alzheimer Disease Research Center with cognitive impairment who were not receiving anti-amyloid treatment.

The researchers found significant changes in 34 proteins with treatment.

"Several markers of Alzheimer's pathology shifted back toward levels found in cognitively healthy individuals, suggesting the treatment was cleaning out amyloid plaques," said Cruchaga, who is also the founding director of the NeuroGenomics and Informatics Center at WashU Medicine.

These included a key marker of the disease, phosphorylated tau, a protein that builds up abnormally in the brains of people with Alzheimer's.

Several proteins related to inflammation also increased. Anti-amyloid drugs work partly by rousing the brain's immune cells, called microglia, and this activation is marked by inflammation.

"Microglia clear amyloid from the brain, so it makes sense that we see higher levels of proteins related to microglial activation," Cruchaga said. "It suggests the treatment is activating the immune system as intended." Importantly, none of the inflammatory changes tracked with faster cognitive decline.

What do blood biomarkers mean for individuals with Alzheimer's disease?

The team identified biomarkers that might eventually inform clinical decisions. One set of biomarkers changed with amyloid clearance, which—if validated—may help clinicians decide how long to treat patients with anti-amyloid therapy. A brain scan is currently the only way to confirm plaques have cleared, but it is unavailable or difficult to access in many places.

A second set of biomarkers was associated with changes in patients' memory and thinking, raising the possibility of a prognostic test that could tell patients and caregivers what to expect. Such tests would indicate the likely pace of the disease, not specifically whether lecanemab is working. Prognostic tests could provide a useful benchmark for all Alzheimer's patients, including those receiving anti-amyloid treatments.

The study was conducted at a single clinic and has not yet been validated elsewhere, which Cruchaga and Schindler described as a major limitation, although they noted that other groups are pursuing similar analyses.

If the findings hold up in other clinics and diverse groups of patients, the researchers anticipate that blood tests to monitor the effects of amyloid-targeting treatments could reach the clinic within a few years.

Publication details

Mu R, et al Dynamic changes in plasma biomarkers in patients treated with lecanemab: a 2-year longitudinal cohort study, The Lancet Neurology (2026). DOI: 10.1016/S1474-4422(26)00284-X

Journal information: Lancet Neurology

Key medical concepts

lecanemabAlzheimer's DiseaseBlood Proteins

Clinical categories

NeurologyLaboratory medicineClinical pharmacology Provided by Washington University in St. Louis Who's behind this story?

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