Lecanemab treatment alters plasma biomarkers in patients with early symptomatic Alzheimer’s disease, driving some molecular concentrations toward those seen in healthy individuals while pushing others in abnormal directions, neurologyadvisor.com reported.
Researchers evaluated 130 plasma proteins in patients receiving intravenous lecanemab at the Washington University Memory Diagnostic Center in St. Louis, Missouri. The longitudinal observational cohort study tracked participants between July 2023 and October 2025.
Eligible patients met criteria for lecanemab treatment and had confirmed amyloid pathology. Participants received intravenous infusions of 10 mg/kg every two weeks. Clinicians obtained blood samples and assessments approximately every six months for up to two years, emjreviews.com reported.
The analysis included 197 patients receiving lecanemab, alongside 1,312 individuals with cognitive impairment who were not treated. This untreated group contained 173 patients prescribed lecanemab who had not yet started therapy. Researchers also evaluated 458 cognitively unimpaired individuals with negative amyloid biomarkers, as detailed by neurologyadvisor.com. Among treated patients, the median age was 73 years, 53% were women, and 98% were White, with 138 individuals having multiple blood samples available for longitudinal analysis.
Researchers classified these responses into four distinct patterns, according to emjreviews.com.
- Levels of phosphorylated tau (p-tau)217, MAPT, and GFAP, for instance, trended back toward the values measured in healthy amyloid β-negative study participants. Before treatment, plasma p-tau concentrations were approximately 130% to 192% higher than control concentrations, and although these levels declined with treatment, they remained 15% to 44% higher after 24 months.
- Overcorrecting: Ten biomarkers, including amyloid-beta peptides Aβ42, Aβ40, and Aβ38, increased beyond concentrations observed in amyloid-negative control participants. Overcorrecting biomarkers moved towards and then beyond those concentrations (eg, amyloid β peptides). Plasma Aβ levels exceeded those of the control group by over 100% at the 18-month mark, with Aβ40 exhibiting the greatest lecanemab-related shift.
- Moving Further Away: Biomarkers associated with inflammatory and neurodegenerative processes moved further from control concentrations. Opposite biomarkers moved further from them (eg, NPTXR, NRGN and TREM2).
- Unchanged: Neurofilament light chain and apolipoprotein E remained stable during treatment. Unchanged biomarkers included NEFL and APOE.
Biomarkers associated with amyloid clearance largely differed from those tracking cognitive outcomes. The estimated adjusted mean CDR-SB increase was 1.2 points at 18 months and 1.6 points at 24 months.
The analysis included 197 patients receiving lecanemab at the Washington University Memory Diagnostic Center.
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