Anti-amyloid therapy offers a natural test of whether cortical quantitative susceptibility mapping (QSM) follows amyloid burden after treatment. We analyzed a real-world lecanemab-treated Alzheimer’s disease cohort with paired imaging. Global Aβ-PET decreased substantially after treatment (ΔCentiloid = −63.8; 95% CI −83.7 to −43.9; P = 3.54e−10; paired Aβ-PET n = 68), confirming amyloid target engagement. In contrast, voxel-weighted cortical QSM increased across paired scans (ΔQSM = +2.85 ppb; 95% CI +2.00 to +3.69; P = 1.95e−09; paired QSM n = 87). In the exact Aβ-PET/QSM overlap sample (n = 67), ΔCentiloid did not explain Δcortical QSM (r = 0.06; 95% CI −0.18 to 0.30; P = 0.632). These data support amyloid-clearance/QSM dissociation during early lecanemab follow-up, without establishing treatment-specific tissue-iron causality.

Keywords: lecanemab; Alzheimer’s disease; anti-amyloid therapy; QSM; Aβ-PET; Centiloid; amyloid clearance; cortical susceptibility.