- Design
- Single-centre longitudinal cohort with untreated and amyloid-negative controls
- Population
- 197 patients with early symptomatic Alzheimer disease on lecanemab
- Primary outcome
- Change in 130 plasma proteins over up to 2 years
- Effect
- 34 changed; p-tau217 and GFAP normalised; TREM2, NPTXR diverged; NfL unchanged
A Lancet Neurology cohort study followed 197 patients receiving lecanemab in routine care at one US centre, with blood every six months for up to two years, and compared 130 plasma proteins with untreated cognitively impaired patients and amyloid-negative controls.
34 proteins changed significantly. p-tau217 and GFAP moved towards normal values. Amyloid β peptides overshot beyond normal. Some inflammatory and synaptic markers, including TREM2, NPTXR and neurogranin, moved further from normal. Neurofilament light did not change.
Plasma p-tau217 is increasingly used for diagnosis, and clinicians are asking whether it can track treatment. These data suggest some markers may serve that role, but others behave in ways not yet understood, possibly reflecting an immune response to plaque removal.
No plasma marker is yet validated for monitoring anti-amyloid treatment. Keep to the label's monitoring, including MRI for amyloid-related imaging abnormalities.
- Do not use plasma p-tau217 to decide whether to continue lecanemab; it is not validated for that
- Keep to scheduled MRI monitoring for amyloid-related imaging abnormalities
- Expect plasma biomarker results to change on treatment if patients have them repeated
- Note that 98% of this cohort was White, limiting how far results generalise
Why it matters
A falling p-tau217 on treatment is tempting to read as response, and that is not yet justified.
Don't overread it
Biomarker change is not cognitive benefit, and this was a single-centre observational study.
The statistics, in plain English
With 130 proteins tested, a false discovery rate below 0.05 controls for the many comparisons, so the 34 changes are unlikely to be chance — but their clinical meaning is still unknown.
Read the rest in the app
You have read your two free briefings this month. The app carries all 27 specialties, every morning, free — and this finding is waiting in it.
Scan to keep reading on your phone. No account needed to start.
Tomorrow morning, before your first patient
One edition a day for neurology, written by the desk, every claim tied to its paper. Six minutes.
Get the app — free