Amyloid PET and Blood Biomarkers for Monitoring Anti-Amyloid Immunotherapy in Alzheimer’s Disease

Background: The clinical adoption of anti-amyloid monoclonal antibodies, including lecanemab and donanemab, has changed Alzheimer’s disease management from primarily symptomatic care toward biologically targeted intervention. This transition supports renewed evaluation of diagnostic and monitoring practices. Although amyloid positron emission tomography (PET) and blood-based biomarkers often show high baseline concordance, recent clinical trial data suggest that these modalities can differ in their timing and magnitude of change during active treatment. This review examines fluid and imaging biomarker trajectories and proposes a practical framework for multimodal monitoring during immunotherapy. Methods: A comprehensive review was conducted in accordance with PRISMA 2020 guidelines to synthesize current evidence on biomarker kinetics during anti-amyloid immunotherapy. The literature search focused on studies published between January 2020 and February 2026. Priority was given to landmark Phase 3 interventional trials of lecanemab (CLARITY AD) and donanemab (TRAILBLAZER-ALZ 2). Additionally, the review examined large-scale observational cohorts for head-to-head biomarker validation (BioFINDER-2) and preclinical concordance (A4, AHEAD 3-45). Results: Baseline diagnostic concordance between plasma phosphorylated tau at threonine 217 (p-tau217) and amyloid PET appears robust in several cohorts, with reported area under the curve values often exceeding 0.90. Yet, fluid and imaging biomarkers may show different temporal profiles during treatment. These kinetic profiles are derived from separate trials using different assays, PET tracers, populations, and dosing paradigms, rather than head-to-head comparisons. Moreover, the specific magnitude and timing of biomarker change should be regarded as trial-specific rather than generalizable across therapies. Notably, change in plasma p-tau217 correlates only moderately with change in amyloid PET at the individual level (r = 0.484), so its kinetics should not be assumed to mirror amyloid PET within individuals. Even though plasma microtubule-binding region tau 243 may provide complementary information about neurofibrillary tangle burden, it requires further validation for treatment monitoring. Conclusions: Fluid and imaging biomarkers can provide complementary information during anti-amyloid immunotherapy. Blood biomarkers may support early pharmacodynamic monitoring. However, they should not be used alone to confirm individual amyloid clearance. Amyloid PET remains important for confirming amyloid pathology and may help assess treatment-specific clearance endpoints when clinically indicated. A multimodal monitoring framework should be applied with attention to assay platform, PET tracer, disease stage, and treatment protocol.