Led by Principal Investigator Reisa Sperling, MD, Director of the Center for Alzheimer Research and Treatment at Brigham and Women’s Hospital (BWH), the Anti-Amyloid Treatment in Asymptomatic Alzheimer’s (A4) study is a landmark international clinical trial evaluating the efficacy of anti-amyloid treatment in preventing memory loss due to Alzheimer’s disease among healthy older adults.
“This really is a novel study, where we are aiming to prevent or slow the onset of AD symptoms in healthy adults with amyloid-beta plaque by providing treatment much earlier in the disease process,” said Dr. Sperling. “If the study shows a benefit in preventing or slowing cognitive decline in study participants, registration of a drug for preclinical AD could occur within the next five years.”
Older individuals eligible for the A4 study have elevated levels of amyloid-beta plaque, as assessed by imaging, but currently are not exhibiting clinical signs of cognitive impairment or dementia. Participants in the study will be randomized to receive solanezumab, an investigational anti-amyloid agent, or a placebo.
Previous studies of solanezumab demonstrated some improvement in patients with mild symptoms of AD, however, no benefit was seen among patients with more advanced AD. The A4 study takes a very different approach aiming to reduce amyloid-beta buildup in the brain before symptoms appear.
More than 60 sites in the United States, Canada, and Australia will screen more than 10,000 older individuals for the A4 study, which will ultimately enroll 1,000 participants. Supported by the National Institute on Aging – part of the National Institutes of Health – the A4 study is expected to last three years.
Healthy older men and women meeting the following criteria may be referred for evaluation for the A4 study:
A companion to the A4 study is the Longitudinal Evaluation of Amyloid Risk and Neurodegeneration (LEARN) study. The LEARN study is a first of its kind study that will follow individuals who do not have elevated levels of amyloid-beta plaque in order to identify other biological changes related to cognitive decline. Information from the study may help to ultimately develop a risk profile to distinguish individuals with normal cognition in the general population who are at risk of eventually developing Alzheimer’s disease. In addition, a subset of participants in the LEARN study will undergo imaging to detect tau protein. Insights gleaned from the LEARN study are expected to help elucidate the findings from the A4 study.
Reisa Sperling, MD
Director, Center for Alzheimer Research and Treatment, Department of Neurology