The topline results for the Anti-Amyloid treatment in Asymptomatic Alzheimer’s disease (A4) study were released today (https://a4study.org). Unfortunately, the drug being investigated, solanezumab, failed to demonstrate a benefit in slowing memory changes in a population of individuals age 65-to-85 who met criteria for preclinical Alzheimer’s disease.
Preclinical Alzheimer’s is a relatively new construct. It includes people who are older and have normal memory performance, but in whom biological tests suggest that the risk for Alzheimer’s disease dementia is high. The A4 study was among the first ever preclinical AD trials, boldly blazing a trail that has now been followed by several other studies, including the open-to-enrollment AHEAD Study (https://www.aheadstudy.org).
Though the trial did not find that solanezumab will be an effective treatment for preclinical disease, the study has already taught the field immense amounts. The study leadership, including academic investigators and Eli Lilly, the maker of solanezumab, made the screening data for the trial publicly available shortly after recruitment had completed. Many important papers, including several by UCI MIND investigators (https://pubmed.ncbi.nlm.nih.gov/35543002/ https://pubmed.ncbi.nlm.nih.gov/34227249/https://pubmed.ncbi.nlm.nih.gov/33336226/ https://pubmed.ncbi.nlm.nih.gov/32777010/ ) have helped advance the field, increasing our understanding of the earliest biological and clinical changes in Alzheimer’s disease and improving the methods for conducting efficient and sensitive trials at the preclinical stage. The full dataset for the entire A4 Study will be made publicly available, giving investigators worldwide the opportunity to use these remarkable data to accelerate discovery.
These advances and those that will come were made possible by the many participants and study partners who gave their time, energy, blood, sweat and tears to the A4 Study. Some people have been in the A4 Study for an amazing 10 years and all of them demonstrated a commitment to the Alzheimer’s disease research mission that is second to none. Words are not adequate to convey our gratitude to these participants and study partners who made A4 possible at UCI MIND and beyond. You are true research heroes, and we are indebted to you. Solanezumab may not be the answer we seek, but we will get there, with the help of champions like you.