Testing Whether Early Treatment Can Change the Course of Alzheimer’s Disease

Reisa Sperling, MD, is using neuroimaging to ask whether anti-amyloid antibody treatment can reverse Alzheimer’s disease pathology before memory loss sets in. “We are going beyond looking for evidence of preclinical Alzheimer’s disease,” Dr. Sperling says, “and are now asking whether, if you intervene at this stage, you can actually change the course of the disease.”

Dr. Sperling, who is Director of the Center for Alzheimer's Research and Treatment (a collaborative venture with Brigham and Women’s Hospital in Boston) has been a pioneer in imaging the brains of healthy volunteers over time, looking for the tell-tale accumulation of amyloid plaques that presage the development of clinical AD. In the Harvard Aging Brain Study, a longitudinal study of 300 subjects which she co-leads with her husband, Dr. Keith Johnson, “we are really focusing on identifying individuals in the preclinical stage of Alzheimer’s disease,” she says. “About a third of healthy volunteers have evidence of amyloid buildup, suggesting they are at risk for cognitive decline over the following decade.”

Those results have led to initiation of a large-scale secondary prevention trial, called Anti-Amyloid Treatment in Asymptomatic Alzheimer’s Disease, or A4, for which Dr. Sperling is Principal Investigator. It will test whether solanezumab, a monoclonal antibody to amyloid, can benefit individuals who are in the early stages of amyloid accumulation, but still cognitively healthy. The three-year trial will enroll 1000 subjects at 60 centers across the country.

“Anti-amyloid treatment trials at the stage of dementia have generally been negative,” Dr. Sperling notes, “and one of the real conundrums in the field is whether amyloid is irrelevant, or whether we are starting a decade too late.” She strongly suspects the latter, likening amyloid’s role in the brain to cholesterol’s role in heart disease. “If you wait to lower it until you have heart failure, it doesn’t do any good—it’s too late.”

While imaging here will provide the screen for patient selection, she says, “I predict there will come a time that amyloid screening,” whether with imaging, smell identification, or other biomarkers, “will not be necessary, because we will treat everybody pre-emptively, in the same way we vaccinate everybody against diseases we may never be exposed to.”

“One of the real strengths here at MGH is that by integrating laboratory science, genetics, cutting-edge imaging, and really good clinical care, we can ask the central questions about Alzheimer’s disease in a unique and really important way,” she says. “It’s an incredible opportunity to synthesize across the disciplines, really get to the heart of the causes of the disease, and ultimately to successful treatment.”