Lecanemab treatment in early Alzheimer’s disease alters 34 out of 130 plasma protein biomarkers across four distinct trajectories over a two-year period, according to a longitudinal cohort study published in The Lancet Neurology. Researchers tracking 197 patients at the Washington University Memory Diagnostic Center found that specific molecular markers either normalize, overcorrect, move in opposite directions, or remain unchanged following bi-weekly infusions of the antibody therapy.
Alongside this clinical evaluation, broader diagnostic frameworks for Alzheimer’s disease continue to evolve through parallel disclosures, such as United States patent literature highlighting specific biomarker combinations like sTNFR2 and amyloid-beta 42 for disease detection.
Washington University Cohort Tracking Biomarker Trajectories
The study led by R. Mu and colleagues included 197 patients with early symptomatic Alzheimer’s disease and confirmed positive amyloid biomarkers. Participants had a median age of 73 years, with 53 percent female and 98 percent White among those with available data. The cohort was evaluated between July 2023 and October 2025 at the Washington University Memory Diagnostic Center. Patients received lecanemab as a 10 mg/kg intravenous infusion every two weeks, with clinical assessments and blood draws occurring approximately every six months for up to two years.
Investigators compared the treated patients against an untreated control group comprising 1,312 participants with cognitive impairment. This control population included 173 patients awaiting lecanemab, participants from the Knight Alzheimer Disease Research Center, and 458 amyloid-beta-negative participants without cognitive impairment. The primary analytical focus measured changes in plasma concentrations of 130 protein biomarkers using regression and mixed-effects models adjusted for patient demographics.
Four Distinct Plasma Protein Pathways Identified
Out of the 130 plasma biomarkers examined, exactly 34 showed statistically significant changes with a false discovery rate below 0.05 in the lecanemab-treated group. These responsive proteins sorted into four distinct trajectories. Normalizing biomarkers shifted toward concentrations typically observed in amyloid-beta-negative individuals without cognitive impairment, including phosphorylated tau 217 (p-tau217), MAPT, and GFAP. Overcorrecting biomarkers moved toward and eventually beyond those normal concentrations, a pattern observed notably in amyloid-beta peptides.
Conversely, opposite biomarkers moved further away from healthy baseline concentrations, including NPTXR, NRGN, and TREM2. Meanwhile, a set of unchanged biomarkers included NEFL and APOE, which did not register significant alteration over the two-year infusion period.
Patents outline protein pairings for Alzheimer's detection
While clinical trials evaluate treatment response through plasma protein shifts, parallel diagnostic methodologies focus on cerebrospinal fluid and blood signatures for early detection. United States patent records outline detection methods utilizing specific protein pairings. Inventors John Allan Todd and Quynh Anh Thuc Lu disclosed diagnostic applications measuring combinations such as sTNFR2 and amyloid-beta 42, as well as sTNFR2 and p-tau181. These patented detection frameworks determine Alzheimer's disease by comparing combined patient concentrations against healthy populations, showing how biomarker science intersects with therapeutic monitoring.
Frequently Asked Questions
How often did patients receive lecanemab infusions in the study?
Patients received lecanemab as a 10 mg/kg intravenous infusion every two weeks for up to two years.
When was the Washington University cohort study conducted?
Patient recruitment and data collection at the Washington University Memory Diagnostic Center took place between July 2023 and October 2025.
How many biomarkers showed significant changes after treatment?
Out of 130 plasma protein biomarkers tested, 34 showed significant changes with a false discovery rate below 0.05 in the lecanemab group.
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