The Right Target at the Right Time in Alzheimer’s Disease

Reisa Sperling by Reisa Sperling

For so many years now, the focus of Alzheimer’s disease (AD) research has been on trying (and failing) to manage Alzheimer’s symptoms at later stages of the disease, rather than preventing these devastating symptoms from developing in the first place. And over the past ten years or so, as we are painfully aware, this approach has left us without any real way to help people who are already suffering with memory problems from progressing to severe dementia. However, these disappointments have not been in vain. Even trials that “fail” to meet their stated goal have given us crucial knowledge that we simply didn’t have ten, five or even two years ago. Combining this information with new imaging methods and other tools that have been successfully developed, the research field is better poised than ever to transform how we deal with AD. Thus, I am very hopeful that “now is the time” to continue seeking treatments, and to try a new approach aimed at preventing memory loss due to AD.

The A4 study – which stands for Anti-Amyloid Treatment in Asymptomatic AD – is an example of that new hope, and its goal is to prevent the memory loss associated with AD in people who are at higher risk, but who are still cognitively normal. The A4 study is for healthy people who may have evidence of being at the very, very earliest stages of developing AD changes in their brains, but whose memories are still intact. This evidence of early AD change is in the form of amyloid plaques that build up in the brain in people with Alzheimer’s disease dementia, and now we can see evidence of these plaques with a special type of brain scan. If we can help the body safely clear out these plaques and prevent amyloid from building up, the hope is that we can protect memory function before it ever falters. And isn’t this the way we now think of cardiovascular disease and cholesterol? Cancer? HIV/AIDS? Diabetes?

The premise of the A4 study is that if we can see the earliest signs of brain changes in PET scans, spinal fluid, MRIs, and other measures and intervene right away, ultimately we can treat and prevent someone from ever proceeding down that path toward dementia. The A4 study is using an investigational drug called solanezumab, which is an antibody that is designed to help the body clear out amyloid. The antibody is infused through an IV drip in the arm each month over about 30 minutes. We will be comparing changes over time in the solanezumab group with the placebo group using cognitive tests and by tracking any evidence of brain damage to see if we are slowing memory decline.

Importantly, A4 also is seeking answers to other questions about AD that science has not yet been able to explain, including why the disease is so much more prevalent in women, and in the African American and Hispanic/Latino communities. Accordingly, the A4 study is committed especially to finding and working with minority participants to help us uncover some crucial clues to these long-standing mysteries.

Overall, what type of people are we looking for? Women and men who:

  • Are between the ages of 65 and 85;
  • Have normal thinking and memory abilities;
  • Have a “study partner” (someone with weekly contact with the study participant, and who is available to answer questions once a year); and
  • Are willing and able to undergo all procedures related to the study over approximately 3 ½ years, and who are dedicated to helping us find the answers!

We believe we will need to screen 10,000 people to find the 1,000 people who are the perfect fit for the A4 study, so finding these individuals is our immediate task. We can use all the help we can get, and engaging the LEAD Coalition and its partner groups and other individuals and organizations across the country will be critical to our success.

I know we can find the answers, and that we must move forward urgently. I have lost a grandfather to this disease, and now I am watching my father battle it. I am absolutely committed to winning this war against AD before my children or grandchildren are ever faced with the same devastating experiences.

Now is the time to join the fight to prevent Alzheimer’s disease. Please help us spread the word! We need your organizations and you personally to help us find the diverse groups of individuals whom might be interested in the A4 study. I am absolutely convinced that we can win this fight, but we need your help to ensure this critical research can get us answers quickly so we can outpace this terrible disease.

Some ways to get the word out:

Share the link/learn more about the A4 Study:

Share the link/watch the A4 video:

Share the link/find an A4 study location near you:

Share additional resources:

 If you would like sample social media content or to discuss other ways you can help, please email us today at or call 844-A4STUDY (844-247-8839).

Dr. Reisa Sperling is a neurologist, specializing in dementia and imaging research. She is a Professor in Neurology at Harvard Medical School; the Director of the Center for Alzheimer Research and Treatment at Brigham and Women’s Hospital; and the Director of the Neuroimaging Core and the Outreach Core of the Massachusetts Alzheimer’s Disease Research Center at Massachusetts General Hospital.    In addition to serving as the Principal Investigator (PI) of the A4 study, Dr. Sperling’s recent work involves the use of functional MRI and PET amyloid imaging to study alterations in brain function in aging and early Alzheimer’s disease. She is also the PI of the Harvard Aging Brain Study, and oversees a number of clinical trials of potential disease-modifying therapeutics in early Alzheimer’s. She has published over 120 peer-reviewed research articles on memory, aging, and early AD.

Disclaimer: The views in guest essays are those of the authors and do not necessarily reflect the views of the LEAD Coalition.