How does APOE4 status affect your clinical decision-making in patients who may be eligible for anti-amyloid therapies for early Alzheimer's disease?  

I feel strongly that persons who are APOE e4 homozygotes have a high enough risk for ARIA to be very discouraging treatment in those individuals. Even with lecanemab, the likelihood of ARIA and therefore premature treatment discontinuation (even without serious consequences of ARIA) ought to give an...

Studies of anti-amyloid therapies show an increased risk of ARIA, both inflammation and bleeding, in patients homozygous for APOE4. This risk is too high to justify the small benefit of these therapies in slowing cognitive deterioration.

APOE4 heterozygotes are offered treatment but cautioned on the increased risk for ARIA and intracranial hemorrhage. APOE4 homozygotes by comparison have an even greater risk and I do not offer them these treatments as an option.

We require ApoE testing before offering treatment with anti-amyloid antibodies. We discuss the risk of ARIA based on ApoE4 status and are in agreement with the phase 3 results and will offer treatment to both heterozygote and homozygote carriers.