PGx lecanemab

APOE encodes apolipoprotein E, a lipid-transport protein central to the clearance and deposition of amyloid beta in the brain. The ε4 isoform is the strongest common genetic risk factor for sporadic and is associated with a greater burden of cerebral amyloid angiopathy. Lecanemab is a humanised monoclonal antibody that binds aggregated amyloid beta. The precise mechanisms underlying amyloid-related imaging abnormalities (ARIA) are not fully understood; treatment-induced changes in vascular amyloid deposits are considered a possible contributing factor. ARIA comprises vasogenic oedema or effusions (ARIA-E) and microhaemorrhages or superficial siderosis (ARIA-H). ARIA risk rises with ε4 dosage. In the pivotal trial reported in the US label, ARIA occurred in 45% of treated ApoE ε4 homozygotes against 22% on placebo, in 19% of heterozygotes against 9%, and in 13% of non-carriers against 4%; symptomatic ARIA-E occurred in 9%, 2% and 1% of treated patients respectively. The relationship is dose-dependent rather than deterministic: the status stratifies the likelihood of ARIA without determining it.

The APOE ε2, ε3 and ε4 isoforms are defined by two coding single-nucleotide variants, rs429358 and rs7412. Genotyping determines both positions and reports the genotype, from which the ApoE ε4 status follows: non-carrier (ε2/ε2, ε2/ε3 or ε3/ε3), heterozygote (one ε4 allele) or homozygote (ε4/ε4).

The result is reported as the APOE genotype and the derived ApoE ε4 status: non-carrier, heterozygote or homozygote. No activity-score framework applies, and the status carries different weight in the two jurisdictions. The EU indication covers non-carriers and heterozygotes with confirmed amyloid pathology, and the product information states that lecanemab is not indicated in homozygotes, so an ε4/ε4 result falls outside the European licence. The US label sets no such limit and instead warns that homozygotes have a higher incidence of ARIA.

The analysis reports only the ε2, ε3 and ε4 isoforms defined by rs429358 and rs7412 and does not detect variants outside these two positions. The genotype is one element of eligibility among several: confirmed amyloid pathology is a further condition of the European indication, and the EU product information excludes patients with MRI findings associated with an increased risk of intracerebral haemorrhage, including previous intracerebral haemorrhage, more than four cerebral microhaemorrhages, superficial siderosis, vasogenic oedema or findings suggestive of cerebral amyloid angiopathy and uncontrolled bleeding disorders; nor is treatment to be initiated under ongoing anticoagulant therapy. ε4 status stratifies ARIA risk but does not exclude it in any genotype group.

The EU product information has the genotype determined with a CE-marked in vitro diagnostic of the corresponding intended purpose or, where none is available, an alternative validated test; separately, treatment is initiated through a central registration system within a controlled access programme. The US label has testing performed before initiation to inform ARIA risk, and adds that a patient may be treated without genotyping, leaving homozygosity undetected.

For current, actionable guidance consult the EMA product information for Leqembi, the US prescribing information for LEQEMBI, and the gene resource.

Results are interpreted in the individual clinical context, and the treatment decision rests with the treating physician.

Content reviewed against the current guidelines on 29 July 2026. Pharmacogenomic classifications are periodically revised; the linked databases above hold the day-current version.

• van Dyck CH, Swanson CJ, Aisen P, Bateman RJ, Chen C, Gee M, et al. Lecanemab in early Alzheimer’s disease. N Engl J Med. 2023;388(1):9-21. PMID: .
• US Food and Drug Administration. LEQEMBI (lecanemab-irmb) prescribing information. BLA 761269, version 24. Boxed warning and section 5.1 Amyloid Related Imaging Abnormalities. Label effective July 21, 2026. Available from:
• European Medicines Agency. Leqembi (lecanemab): EPAR product information. Sections 4.1 Therapeutic indications, 4.3 Contraindications and 4.4 Special warnings and precautions for use. Current June 19, 2026. Available from: