Lecanemab, Donanemab & the Drug Era
The first disease-modifying drugs
For 40 years, Alzheimer's drugs (donepezil, memantine) treated symptoms without touching the underlying disease. That changed in 2021–2024 with the approval of aducanumab, lecanemab (Leqembi), and donanemab (Kisunla) — the first antibodies that meaningfully clear amyloid plaques from the brain.
Lecanemab — CLARITY-AD results
Lecanemab (biweekly IV infusion) slowed clinical decline by ~27% over 18 months in early Alzheimer's. It doesn't reverse symptoms — it buys time, delaying disability onset. Side effects include ARIA (amyloid-related imaging abnormalities) — brain swelling or microbleeds that require MRI monitoring.
Donanemab — TRAILBLAZER-ALZ 2
Donanemab (monthly IV) clears amyloid more completely and once plaque is gone, treatment can potentially stop. TRAILBLAZER-ALZ 2 showed ~35% slowing in low-tau patients, less in higher-tau groups. Like lecanemab, it requires MRI monitoring for ARIA. Approved 2024.
The APOE4 catch
Both drugs carry higher ARIA risk in APOE4 homozygotes. Lecanemab's label recommends APOE testing before treatment. For APOE4/4 patients (2–3% of population) the risk-benefit calculation is different. Knowing your APOE status matters most here — it directly changes what therapies you're a candidate for.
ARIA — the side effect to know
Amyloid-Related Imaging Abnormalities (ARIA) — micro-bleeds and edema in the brain — occur in 20-30% of patients on lecanemab/donanemab, mostly in the first 6 months. Most are asymptomatic and resolve with dose pauses. Severe ARIA is rare but can be life-threatening. Two important risk factors: APOE4 homozygous status (3-4× higher risk) and concurrent anticoagulants. This is why MRI monitoring + APOE genotyping are required before starting these drugs.
Key Takeaway
After decades of failed trials, the amyloid-targeting antibodies have cleared the bar of disease modification — modestly. They're expensive, require infusions + MRI monitoring, and work best in early disease. This is the beginning, not the end, of the Alzheimer's drug era. Early detection now has a treatment to point to.