APOE ε4 genotype-dependent reduction of amyloid-related imaging abnormality in real-world lecanemab use: Implications for risk-stratified prescribing.

Real-world amyloid-related imaging abnormality (ARIA) rates with lecanemab are consistently lower than in the Clarity AD trial, yet whether this reduction is genotype-specific is unknown. We compared published APOE ε4-stratified ARIA-E and ARIA-H rates from Clarity AD with a US real-world cohort and Japanese post-marketing surveillance. ARIA rates were largely unchanged in APOE ε4 noncarriers, whereas reductions were concentrated among carriers, especially homozygotes. This pattern was observed for both ARIA subtypes across both settings. These early real-world findings suggest that the apparent attenuation of ARIA during the initial clinical introduction of lecanemab is consistent with genotype-informed risk selection rather than a uniform population-wide decrease.