Impact of genetic variation on response to therapy
Patients who are carriers of the APOE4 variant of the APOE gene (also called the APOE ε4 allele) have a higher frequency of Amyloid Related Imagine Abnormalities (ARIA) including oedema/effusions, haemorrhage/haemosiderin deposition, microhaemorrhage and cortical superficial siderosis when treated with donanemab compared to non-carriers. APOE4 carriers have a higher frequency (homozygotes greater than heterozygotes) of ARIA compared to non-carriers.
The SmPC for donanemab states that donanemab 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 donanemab 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 homozygotes
- Higher risk of ARIA compared to heterozygous carriers or non-carriers.
- Do not use donanemab.
APOE4 heterozygous carriers
- Lower risk of ARIA compared to APOE4 homozygotes, but higher than non-carriers.
- Initiate and titrate in accordance with manufacturer’s instructions (consult the SmPC).
APOE4 non-carriers
- Lower risk of ARIA compared to APOE4 homozygotes and heterozygous 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
Eli Lilly and Company Limited (2024) Kisunla 350mg concentrate for solution for infusion SmPC. Available at: https://www.medicines.org.uk/emc/product/16014/smpc (Accessed online: 13th February 2026).
