Impact of genetic variation on response to therapy
Patients who are homozygous for the APOE4 variant of the APOE gene (also called the APOE ε4 allele) have a higher incidence of Amyloid Related Imagine Abnormalities (ARIA) including brain oedema, sulcal effusions, microhaemorrhage and superficial siderosis when treated with lecanemab compared to heterozygous carriers and non-carriers.
The SmPC for lecanemab states that lecanemab is indicated for the treatment of mild cognitive impairment and mild dementia due to Alzheimer’s disease only in adult patients that are APOE4 heterozygous carriers or non-carriers.
Testing recommendations
The SmPC for lecanemab states that testing for APOE4 status should be performed prior to treatment initiation.
Therapeutic recommendations
Treatment should be initiated and supervised by physicians experienced in the diagnosis and treatment of Alzheimer’s disease.
APOE4 homozygous carriers
- Higher risk of ARIA compared to heterozygous carriers or non-carriers.
- Do not use lecanemab.
APOE4 heterozygous carriers or non-carriers
- Lower risk of ARIA compared to homozygous carriers.
- Initiate and titrate in accordance with manufacturer’s instructions (consult the SmPC).
Further information
APOE gene variants including APOE4 have been identified as risk variants for Alzheimer’s disease. Prior to testing, patients should be appropriately counselled and consented according to national or local guidelines.
References
Eisai Ltd (2024) Leqembi 100mg/ml concentrate for solution for infusion SmPC. Available at: https://www.medicines.org.uk/emc/product/15908/smpc (Accessed online: 13th February 2026).
