Clinical Reference · Cognitive Neurology · Therapeutics

Anti-Amyloid Therapies for Alzheimer Disease

The monoclonal antibodies, who qualifies, and the safety that governs their use
Lecanemab
Leqembi · anti-protofibril mAb (Eisai/Biogen)
FDA traditional approval Jul 2023
~27% slowing of decline (CDR-SB, 18 mo) — CLARITY AD
Target
Soluble amyloid protofibrils
Dosing
10 mg/kg IV every 2 weeks
ARIA
ARIA-E ~13% (higher in APOE ε4 homozygotes)
Donanemab
Kisunla · anti-plaque (N3pG) mAb (Eli Lilly)
FDA approval Jul 2024
~35% slowing (low/medium tau) — TRAILBLAZER-ALZ 2
Target
Deposited plaque (pyroglutamate Aβ)
Dosing
IV every 4 weeks; can STOP after plaque clearance
ARIA
ARIA-E ~24%; higher with ε4
Aducanumab
Aduhelm · anti-aggregated Aβ mAb (Biogen)
Accelerated 2021 → withdrawn 2024
Discontinued
Controversial — EMERGE positive, ENGAGE negative; market-withdrawn
Target
Aggregated Aβ (fibrillar + oligomer)
Status
No longer available — development discontinued 2024
Legacy
First amyloid-clearing approval; set the ARIA-monitoring precedent
Who Qualifies
Eligibility & pre-treatment workup
Early symptomatic AD only
MCI–mild AD dementia with confirmed amyloid — not moderate/severe
Confirm Amyloid
Amyloid PET or CSF Aβ42:40 + p-tau (required)
Genotype
Test APOE first — ε4 homozygotes carry the highest ARIA risk
Baseline MRI
Exclude >4 microhemorrhages, macrohemorrhage, superficial siderosis
ARIA
Amyloid-related imaging abnormalities
The defining safety issue
Edema (ARIA-E) & microhemorrhage/siderosis (ARIA-H)
Risk
Highest in APOE ε4 homozygotes & early in treatment
Monitor
Surveillance MRI before specified infusions; mostly asymptomatic
Warning
Can cause headache, confusion; rarely serious/fatal — hold for symptomatic ARIA
Practical Use
Cautions & counseling
Benefit = slowing, not reversal
Modest slowing of decline — set expectations vs cost & infusion burden
Caution
Anticoagulation ↑ ARIA-H bleed risk; caution with recent stroke / tPA
Avoid
No confirmed amyloid; significant CAA / multiple microbleeds
Counsel
Real but small clinical benefit; ongoing MRI monitoring commitment
⚡Before the first infusion
Confirm amyloid (PET or CSF), genotype APOE, and get a baseline MRI — eligibility and ARIA risk both hinge on these.
🩸Watch the bleed risk
ARIA-H + anticoagulation is a dangerous combination; symptomatic ARIA means hold the drug and re-image.
Sources: Neuro.Wiki › Cognitive Neurology / Therapeutics. CLARITY AD (van Dyck 2023) · TRAILBLAZER-ALZ 2 (Sims 2023) · FDA labels (Leqembi, Kisunla) · AppropriateUse recommendations. Educational reference — not medical advice; verify current labeling & local protocols. Neuro.Wiki