AMONG PATIENTS with early symptomatic Alzheimer’s disease, lecanemab treatment has been linked to dynamic, multidirectional changes in plasma biomarkers, with partial normalisation of amyloid and tau markers alongside abnormal inflammatory and neurodegeneration-related concentrations, new research has found.
This longitudinal cohort study included 197 patients with early symptomatic Alzheimer’s disease and positive amyloid biomarkers (median age 73 years; 53% female; 98% White among those with available data) who were eligible for lecanemab under the FDA label and consented to blood collection at the Washington University Memory Diagnostic Center between July 2023 and October 2025.
Lecanemab was given as a 10 mg/kg intravenous infusion every 2 weeks, with assessments and blood draws about every 6 months for up to 2 years. Untreated controls comprised 1312 participants with cognitive impairment, including 173 patients awaiting lecanemab and Knight Alzheimer Disease Research Center participants, and 458 amyloid β-negative participants without impairment.
The primary outcome was change in plasma concentrations of 130 protein biomarkers, examined using regression and mixed-effects models adjusted for demographics.
Of the 130 plasma biomarkers, 34 showed significant changes (false discovery rate below 0.05) in the lecanemab group, and the biomarkers fell into four trajectories. Normalising biomarkers shifted towards concentrations seen in amyloid β-negative individuals without cognitive impairment (eg, phosphorylated tau [p-tau]217, MAPT and GFAP). Overcorrecting biomarkers moved towards and then beyond those concentrations (eg, amyloid β peptides). Opposite biomarkers moved further from them (eg, NPTXR, NRGN and TREM2), while unchanged biomarkers included NEFL and APOE.
These divergent trajectories suggest that different plasma biomarkers could eventually serve different clinical purposes, such as monitoring treatment responses or informing prognosis, although further validation remains needed. Additionally. the abnormal inflammatory and neurodegeneration-related changes might reflect an immune response to amyloid plaques and treatment effects on neuronal and synaptic processes distinct from amyloid clearance.
Reference
Mu R et al. Dynamic changes in plasma biomarkers of Alzheimer’s disease in patients treated with lecanemab: a longitudinal cohort study. The Lancet Neurology. 2026;DOI:10.1016/S1474-4422(26)00284-X.
Featured image: PaeGAG on Adobe Stock
PaeGAG on Adobe Stock
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