A major milestone was the launch of the Anti-Amyloid treatment in Asymptomatic Alzheimer’s (A4) Study. A4 is the first multicenter trial in sporadic preclinical (pre-symptomatic) Alzheimer’s disease (AD). The idea for this project arose from analysis of longitudinal observational data from the Alzheimer’s Disease Neuroimaging Initiative (ADNI) that indicated that amyloid elevation in brain in clinically normal individuals is associated with subtle cognitive and biomarker evidence of decline. Thus ‘preclinical AD’ may be the optimal stage at which to intervene with anti- amyloid therapies, with sensitive cognitive tests as well as secondary biomarker measurements as outcomes to establish efficacy. A4 was initially funded as a project of the ADCS. Solanezumab, a monoclonal antibody against monomeric amyloid peptide was selected as the therapeutic, and a public private partnership with Eli Lilly and NIA was established to carry out the trial, with additional funding contributed by philanthropic groups. A4 transitioned to USC ATRI in 2015 and was fully enrolled with 1169 randomized participants across 67 sites by the end of 2017. It will be completed near the end of 2022. In a first for a Phase 3 trial, A4 pre- randomization data, which provides the largest dataset on amyloid accumulation in clinically normal individuals, was publicly released one year after completion of enrollment.