Lecanemab Treatment Triggers Dynamic Changes in Alzheimer’s Plasma Biomarkers
In patients with early symptomatic Alzheimer’s disease, lecanemab treatment produces dynamic and multidirectional changes in plasma biomarkers, according to a longitudinal cohort study published in The Lancet Neurology. Researchers found that while amyloid and tau markers show partial normalization, concurrent changes in inflammatory and neurodegeneration-related concentrations indicate complex biological responses beyond simple plaque clearance.
The study evaluated 197 patients with early symptomatic Alzheimer’s disease and positive amyloid biomarkers. Conducted at the Washington University Memory Diagnostic Center between July 2023 and October 2025, the research tracked participants eligible for lecanemab under the FDA label who consented to regular blood collections. Patients received lecanemab as a 10 mg/kg intravenous infusion every two weeks, undergoing clinical assessments and blood draws approximately every six months for up to two years.
Comparison With Untreated Control Groups
To establish baseline trajectories and control for natural disease progression, investigators compared the treatment group against 1,312 untreated participants with cognitive impairment. This control cohort included 173 patients awaiting lecanemab treatment, participants from the Knight Alzheimer Disease Research Center, and 458 amyloid-beta-negative participants without cognitive impairment.
Researchers examined changes across 130 plasma protein biomarkers using regression and mixed-effects models adjusted for demographic variables. Out of the 130 proteins evaluated, 34 demonstrated statistically significant changes, registering a false discovery rate below 0.05 within the lecanemab-treated cohort.
Four Distinct Biomarker Trajectories Identified
The 34 significantly altered biomarkers separated into four distinct trajectories following treatment initiation:
- Normalizing biomarkers: Protein concentrations shifted back toward levels observed in amyloid-beta-negative individuals without cognitive impairment. Examples include phosphorylated tau (p-tau) 217, MAPT, and GFAP.
- Overcorrecting biomarkers: Concentrations moved toward and subsequently surpassed the baseline levels of healthy controls. Amyloid-beta peptides exemplified this trajectory.
- Opposite biomarkers: Concentrations moved further away from healthy control levels. This group included NPTXR, NRGN, and TREM2.
- Unchanged biomarkers: Levels remained stable despite treatment. This category featured NEFL and APOE.
Plasma Biomarkers May Track Patient Responses to Therapy
These divergent trajectories suggest that specific plasma biomarkers could eventually fulfill different clinical roles, such as tracking individual patient responses to therapy or informing long-term prognoses. However, the study authors emphasize that further clinical validation remains necessary before these markers guide routine care.
The abnormal inflammatory and neurodegeneration-related shifts observed in the blood samples may reflect an active immune response directed at amyloid plaques. These alterations likely point to treatment effects on neuronal and synaptic processes that operate independently of direct amyloid clearance.
How Lecanemab Infusions and Patient Demographics Affected Biomarkers?
How often did patients receive lecanemab infusions during the study?
Participants received lecanemab as a 10 mg/kg intravenous infusion every two weeks throughout the duration of the monitoring period.
What was the demographic makeup of the lecanemab-treated cohort?
The cohort had a median age of 73 years, consisted of 53% female participants, and was 98% White among those with available demographic data.
Which specific biomarkers showed a normalizing trajectory?
Biomarkers including phosphorylated tau (p-tau) 217, MAPT, and GFAP shifted back toward concentrations typically found in amyloid-beta-negative individuals without cognitive impairment.
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