Does oral valiltramiprosate slow clinical decline and brain atrophy in APOE4/4 homozygotes with early Alzheimer's disease without causing ARIA?
Can crenezumab, started before symptom onset, prevent or delay cognitive decline in cognitively unimpaired PSEN1 Glu280Ala mutation carriers predestined to develop autosomal-dominant Alzheimer's disease?
API ADAD Colombia
Safety and efficacy of crenezumab in cognitively unimpaired carriers of the PSEN1 Glu280Ala mutation at risk for autosomal-dominant Alzheimer's disease in Colombia (API ADAD Colombia Trial): a phase 2, randomised, double-blind, placebo-controlled trial
Lancet Neurology · 2026
Bottom Line: Crenezumab administered for 5–8 years did not prevent or delay cognitive decline in preclinical autosomal-dominant Alzheimer's disease; robust fibrillar amyloid removal — not achieved by crenezumab — appears necessary for clinical efficacy, and future prevention trials should prioritize agents with demonstrated potent amyloid-clearing capacity.