- Design
- Longitudinal observational cohort with untreated and amyloid-negative comparison groups
- Population
- 197 patients with early symptomatic Alzheimer's disease on lecanemab
- Primary outcome
- Change in 130 plasma protein biomarkers
- Effect
- 34 changed significantly (FDR <0.05); p-tau217 and GFAP normalised; TREM2, NPTXR moved away
This cohort followed 197 people with early symptomatic Alzheimer's disease on lecanemab in routine care at Washington University, with blood samples about every six months for up to two years. They were compared with untreated cognitively impaired patients and amyloid-negative controls. A panel of 130 plasma proteins was measured.
Thirty-four proteins changed significantly on treatment, in four patterns. p-tau217, MAPT and GFAP moved towards normal. Amyloid peptides overshot normal. TREM2, NPTXR and neurogranin moved further from normal. Neurofilament light and APOE did not change.
The practical point is that 'the biomarker' after anti-amyloid therapy is not one thing. Plasma p-tau217 may become a way of tracking treatment response, while the inflammatory and synaptic changes may reflect the immune response to plaque clearance. None of this is validated for guiding individual treatment yet.
- Do not use plasma biomarkers to decide whether to continue lecanemab in an individual patient yet.
- Expect plasma p-tau217 to fall towards normal on treatment; this is not proof of clinical benefit.
- Unchanged neurofilament light means it is not a useful marker of treatment response here.
- Recognise that anti-amyloid therapy triggers immune and synaptic changes whose meaning is unknown.
Why it matters
It suggests blood tests could eventually monitor anti-amyloid therapy, and shows they will not all move together.
Don't overread it
This single-centre cohort was almost entirely White and did not link biomarker changes to clinical outcomes.
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