Josephine and John Marr Alzheimer's Research Fund

Josephine and John Marr Alzheimer's Research Fund

"We need to act now to uncover the treatments and cures that will help our children and our children's children." —John Marr

Josephine and John Marr Alzheimer's Research Fund


Alzheimer prevention initiative

Thanks to more than 30 years of research, we now know that the brain abnormalities responsible for Alzheimer’s disease begin decades before the onset of clinical symptoms. The Anti-Amyloid Treatment in Asymptomatic Alzheimer’s Disease (A4) Study, led by BWH neurologist Reisa A. Sperling, MD, MMSc, and other national leaders, builds on these insights.

Watch Reisa A. Sperling, MD, MMSc, present research findings and advances in Alzheimer’s disease

The A4 Study is the first trial to investigate whether a drug can reduce amyloid plaque buildup in the brain—a hallmark of the disease—and thereby stop the disease from progressing in older individuals, ages 65-85, who have elevated levels of amyloid plaque in their brain but do not yet show any symptoms of memory loss. The A4 Study uses an anti-amyloid treatment based on more than three decades of pioneering research by BWH neurologist and neuroscientist, Dennis J. Selkoe, MD. The goal is to prevent memory loss associated with Alzheimer’s disease through a strategy known as secondary prevention.

But the Marr family—together with Sperling, Selkoe, and their colleagues at BWH—are focused on finding a way to stop Alzheimer’s disease altogether through earlier intervention that will prevent amyloid from ever accumulating in the brain. This forward-thinking endeavor represents a critical next step as we shift the focus to the earliest phase in the disease trajectory.

Bending the Curve: Advances in Research

The Josephine and John Marr Alzheimer’s Research Fund is bringing BWH closer to bending the curve and conducting clinical studies in middle-age individuals at risk. Support is already fueling a comprehensive research approach that brings more than 100 expert physicians and scientists together under the leadership of Sperling and Selkoe.

Recognizing that understanding early disease mechanisms in Alzheimer’s is essential to identifying pathways toward prevention, collaborations span research in advanced neuroimaging, refinements in cognitive testing, blood and cerebrospinal fluid biomarker identification and validation, and genetics. Importantly, this also includes building an observational cohort of individuals younger than age 65—who do not yet show elevated levels of amyloid plaque in their brains but are at risk for Alzheimer’s due to family history or other reasons. The knowledge gained from this group will become a study platform for future clinical trials to prevent Alzheimer’s. The work is translational: discoveries in the lab will inform work in the clinical space, and insights from clinical research will in turn provide new avenues for exploration in the lab.

These ambitious goals require support during a number of years, but pushing boundaries is critical to achieving change. With decades of research and technological advances, BWH is at a pivotal point where a true Alzheimer’s prevention initiative is possible—and the visionary support of the Josephine and John Marr Alzheimer’s Research Fund is making it a reality.


Dennis J. Selkoe, MD
Co-director, Ann Romney Center for Neurologic Diseases, Brigham and Women’s Hospital
Coates Professor of Neurologic Diseases, Harvard Medical School

Dennis J. Selkoe, MD, is co-director of the Ann Romney Center for Neurologic Diseases at Brigham and Women’s Hospital and the Coates Professor of Neurology at Harvard Medical School (HMS) . After graduating from Columbia University with a BA and the University of Virginia with an MD, he trained at the National Institutes of Health, the Harvard/Longwood Neurology Program, and the HMS Department of Neuroscience. Selkoe and his colleagues isolated the tangles of Alzheimer’s disease (AD) and co-discovered their antigenic relationship to tau. His research on amyloid ß-protein and APP led him to formulate the amyloid hypothesis of AD, which has helped provide the underpinning of numerous clinical trials, including A4, the world’s first prevention trial in older individuals at risk for developing Alzheimer’s disease. His lab discovered that Aß is produced by cells throughout life, enabling the dynamic study of Aß generation and screens for inhibitors. They showed that APP and presenilin mutations cause AD by altering Aß production. With Michael Wolfe, PhD, Selkoe identified presenilin as the gamma-secretase, the first intramembrane aspartyl protease in biology. Selkoe has received many honors for his work, including the Pioneer Award and Lifetime Achievement Award from the Alzheimer’s Association. He was the principal founding scientist of Athena Neurosciences, and is now a founding director of Prothena Biosciences.

Reisa A. Sperling, MD, MMSc
Director, Center for Alzheimer’s Research and Treatment (CART)
Brigham and Women’s Hospital

Reisa Sperling MD, MMSc, is a neurologist specializing in dementia and imaging research and a professor of neurology at Harvard Medical School. Sperling’s research is focused on the early diagnosis and treatment of Alzheimer’s disease. Her recent work involves the use of MRI and PET imaging to detect the earliest brain changes of Alzheimer’s disease, and improve our understanding of why memory changes in aging. She is the principal investigator of the Harvard Aging Brain Study, a pioneering observational study to determine the factors that allow older individuals to maintain healthy brain function as well as to discover the biomarkers that predict memory decline. Sperling led the National Institute on Aging and Alzheimer’s Association Workgroup to develop international guidelines for research on the preclinical stage of Alzheimer’s disease. She serves as the project director of the Anti-Amyloid Treatment in Asymptomatic Alzheimer’s disease (A4) Study, a landmark secondary prevention trial in over 1000 clinically normal older individuals at risk for memory decline due to Alzheimer’s disease. Sperling was honored with the American Academy of Neurology Potamkin Award in 2015.