Alzheimer's Disease: From Hypothesis to Treatment

SignalMoss  ·  Science  ·  May 23, 2026

Risk shown as multiplier vs APOE3/3 baseline (most common genotype, ~78% of population). Hover each bar for detail. Sources: Corder et al. 1993; Genin et al. 2011 (Mol Psychiatry).

Click any event to expand detail. Gray nodes mark periods of trial failure. Sources: FDA approval records; NEJM; Indiana University School of Medicine.

Lecanemab
Leqembi  ·  Eisai / Biogen
TargetAmyloid-beta protofibrils
TrialCLARITY AD — 1,795 patients
Efficacy27% slower decline vs placebo
ARIA-E riskModerate — 21%
FDAApproved Jul 2023
EMAApproved (restricted)
DosingIV infusion every 2 weeks
Donanemab
Kisunla  ·  Eli Lilly
TargetN3pG amyloid-beta form
TrialTRAILBLAZER-ALZ 2 — 1,736 patients
Efficacy35% slower decline vs placebo
ARIA-E riskHigher — 36%
FDAApproved Jul 2024
EMARejected — risk/benefit
DosingIV every 4 weeks; stop when amyloid cleared

ARIA-E = amyloid-related imaging abnormalities (oedema). Risk is higher in APOE4 carriers for both drugs. Sources: NEJM 2022 (lecanemab); NEJM 2023 (donanemab); FDA prescribing information.

Sources: Lecanemab Trial — NEJM · Donanemab Trial — NEJM · APOE4 Risk — Mol Psychiatry · SignalMoss, May 2026