Regional amyloid‐PET clearance dynamics and anti‐Aβ monoclonal antibody therapy: a preliminary real‐world study

Abstract INTRODUCTION Amyloid positron emission tomography (PET) is the reference biomarker for treatment target engagement in anti‐amyloid beta (Aβ) therapies in early symptomatic Alzheimer's disease (AD), yet global metrics may mask a regional heterogeneity of amyloid clearance. METHODS We report real‐world longitudinal amyloid‐PET data from 26 patients treated with lecanemab or donanemab for 6 months. Global Centiloids and regional standardized uptake value ratios (SUVRs) were quantified at baseline and 6 months and examined according to treatment, clinical diagnosis, and clinical stage. RESULTS Amyloid removal was regionally heterogeneous. Patients with mild cognitive impairment showed greater cortical amyloid reduction than those with mild dementia, while early‐ and late‐onset AD exhibited comparable clearance. Frontal, anterior cingulate, and parietal regions showed the largest SUVR reductions, whereas the occipital cortex and temporal mesial cortex were consistently spared, including in patients reaching global amyloid‐PET negativity. DISCUSSION Early amyloid clearance following anti‐amyloid treatment is regionally heterogeneous and incompletely captured by global PET measures.