JAMA Neurol

Lower amyloid levels after donanemab tied to slower Alzheimer’s progression

October 17, 2025

Study details: This post hoc exploratory analysis of the phase 3 TRAILBLAZER-ALZ 2 trial (NCT04437511) included 1,582 participants (mean age, 72.9 years; 56.9% female) with early symptomatic Alzheimer disease and confirmed amyloid and tau pathology. Patients were randomized 1:1 to donanemab (700 mg ×3 doses, then 1400 mg) or placebo every 4 weeks for up to 72 weeks, with outcomes assessed through 76 weeks. Participants were grouped into deciles by lowest posttreatment amyloid PET value.

Results:

• Lower posttreatment amyloid levels correlated with slower decline on the integrated Alzheimer's Disease Rating Scale (R² = 0.73) and Clinical Dementia Rating-Sum of Boxes score (R² = 0.87), and with reductions in plasma p-tau217 (R² = 0.86), p-tau181 (R² = 0.88), and glial fibrillary acidic protein (R² = 0.87).
• No correlation was observed with neurofilament light chain (R² = 0.03).
• Donanemab-treated patients achieved substantially lower amyloid levels than placebo.

Clinical impact: Findings support amyloid plaque removal as donanemab’s mechanism of action and suggest posttreatment amyloid level as a potential surrogate biomarker for clinical benefit in amyloid-targeting therapies.

Source:

Lu M, et al. (2025, October 13). JAMA Neurol. Posttreatment Amyloid Levels and Clinical Outcomes Following Donanemab for Early Symptomatic Alzheimer Disease: A Secondary Analysis of the TRAILBLAZER-ALZ 2 Randomized Clinical Trial. https://pubmed.ncbi.nlm.nih.gov/41082199/