Drugs
Treatments and what they mean for ε4/ε4
APOE genotype matters most for the safety of anti-amyloid antibodies. Several newer approaches target APOE4 biology directly.
Approved for early Alzheimer’s
| Drug | Type | For ε4/ε4 |
|---|---|---|
| Lecanemab (Leqembi) | Anti-amyloid antibody, IV or subcutaneous | Higher risk of ARIA in ε4/ε4. In the US, a boxed warning applies and APOE testing is advised before treatment. In the EU (April 2025), approved only for people who are not ε4 homozygotes. |
| Donanemab (Kisunla) | Anti-amyloid antibody, IV | Higher risk of ARIA in ε4/ε4. The FDA approved a slower dose titration that lowered ARIA-E, most in ε4/ε4 (TRAILBLAZER-ALZ 6). In the EU (September 2025), approved only for people who are not ε4 homozygotes. |
| Donepezil, rivastigmine, galantamine, memantine | Symptomatic treatments | Treat symptoms; do not slow the disease. Used regardless of APOE genotype. |
Investigational, aimed at ε4/ε4
| Drug | Type | For ε4/ε4 |
|---|---|---|
| Valiltramiprosate (ALZ-801) | Oral; blocks formation of toxic amyloid oligomers | Phase 3 APOLLOE4 in ε4/ε4 missed its primary endpoint; a prespecified MCI subgroup favored drug. Low ARIA. |
| LX1001 | Gene therapy that adds the protective APOE2 form | Phase 1/2 in ε4/ε4; early biomarker signals, no ARIA in interim data. FDA Fast Track. |
| HT-4253 | Oral LRRK2 inhibitor acting on the RAB10 pathway | Phase 2a prevention trial in biomarker-positive ε4 carriers planned; not yet recruiting. |
Earlier-stage approaches
| Drug | Type | For ε4/ε4 |
|---|---|---|
| APOE4-targeting antibodies | Antibodies that bind APOE4, such as HAE-4 | Reduce amyloid and tau pathology in animal models; not yet in clinical trials as far as published reports show. |
| APOE4 lowering | Antisense oligonucleotides and gene silencing | Aim to reduce APOE4 production; in preclinical or early development. |
| APOE2 plus APOE4 silencing | Gene therapy (for example Lexeo’s LX1020) | Adds protective APOE2 while suppressing APOE4; preclinical. |
| Gene editing | CRISPR-based conversion of APOE4 | Proof-of-concept studies only; efficiency must improve before clinical use. |
Stopped or withdrawn
| Drug | Type | For ε4/ε4 |
|---|---|---|
| Aducanumab (Aduhelm) | Anti-amyloid antibody | Discontinued by the manufacturer in 2024. |
| Umibecestat (CNP520) | BACE inhibitor | Stopped in 2019 in Generation Studies after mild cognitive worsening. |
| CAD106 | Active amyloid vaccine | Generation Study 1 arm halted in 2019 with the rest of the program. |
This site is for education and is not medical advice. Talk with your doctor or a genetic counselor about your own situation.