Alzheimer’s disease damages the nerve cells in the brain that are responsible for cognition. This damage occurs in association with the deposit of beta amyloid, a normally metabolized protein. However, for people with Alzheimer’s, beta amyloid is processed in an abnormal fashion, making it toxic to the neurons in the brain.
Worldwide, about 40 million people suffer from Alzheimer’s. Without a major medical breakthrough, this brain disorder may plague up to 120 million people by 2050. Existing therapies for Alzheimer’s disease often provide patients with some symptomatic relief for a period of time. However, there are no treatments that change the underlying process of the disease and slow its progression.
Thanks in part to work at Brigham and Women’s Hospital (BWH), we now know the brain abnormalities caused by Alzheimer’s begin over a decade before symptom onset. BWH has been at the forefront of Alzheimer’s research for decades, and is now spearheading the world’s first prevention trial in older individuals at risk for developing the disease. The Anti-Amyloid in Asymptomatic Alzheimer’s (A4) trial is under the direction of Dr. Reisa Sperling at BWH and originates from research within the Ann Romney Center for Neurologic Diseases. The results of this study could fundamentally change the way we treat the hundreds of millions of people at risk for Alzheimer’s around the world.
“My hope is that the Ann Romney Center goes down in history as the place where cures for MS, Alzheimer’s, ALS, and other devastating
neurologic diseases were first discovered.” —Ann Romney
For information about ALS and associated resources at BWH, visit: http://www.brighamandwomens.org/Departments_and_Services/neurology/services/neuromuscular/services/amyotrophic-lateral-sclerosis.aspx
PROMISING ADVANCES TOWARD A BLOOD TEST FOR ALZHEIMER’S DISEASE
Dennis Selkoe, MD, continues to advance efforts to identify and validate Alzheimer’s disease (AD) biomarkers, then leverage those discoveries toward new tools for diagnosis, monitoring, and treatment. Using the most sophisticated technology available, Dr. Selkoe and his colleague, Dominic Walsh, PhD, are working to detect proteins in the blood or cerebrospinal fluid that could serve as biomarkers for AD, including tau, the protein that makes up the “tangles” that accumulate in the brain and impair cognitive function in AD. They were able to successfully measure elevated tau levels in blood samples, suggesting that it may become possible to detect AD with a simple blood test. Such a test offers the potential to detect AD even before symptoms develop, an extraordinary breakthrough that would allow for earlier intervention and improved outcomes in countless patients, as well as streamlined clinical trials.
THE A4 STUDY: THE FIRST-EVER PREVENTIVE CLINICAL TRIAL FOR ALZHEIMER’S DISEASE
Reisa Sperling, MD, MMSc, director of the Center for Alzheimer Research and Treatment (CART) at BWH, is leading the groundbreaking Anti-Amyloid Treatment in Asymptomatic Alzheimer’s Disease (A4) Study, aimed at preventing memory loss due to Alzheimer’s. Using leading-edge brain scan technology to identify and track early amyloid buildup that can occur for decades before symptom onset, the study will test the use of solanezumab—an investigational anti-amyloid antibody—in patients who have no outward symptoms yet but show signs of amyloid accumulation in the brain. One thousand participants across more than 60 sites in the U.S., Canada, and Australia will be monitored for three and a half years to track the earliest stages of memory loss, allowing researchers to determine whether solanezumab can help the brain to clear the amyloid, thereby treating the disease before symptoms ever develop. This multicenter, collaborative effort will help deepen our understanding of how Alzheimer’s progresses and offer new hope for disease prevention.
WORKING TOWARD A VACCINE FOR ALZHEIMER’S DISEASE
Together with their teams, Dr. Weiner and Dennis Selkoe, MD, are currently investigating the development of a nasal spray aimed at clearing the brain of the amyloid proteins responsible for forming the characteristic plaques that impair memory and cognitive function in Alzheimer’s disease. Building upon a decade of research in which Dr. Weiner also called upon his expertise in MS to understand related biological processes and refine the vaccine, the team has honed in on a substance called protollin that enhances the body’s immune response. This research is showing promising results in the lab. Drs. Weiner and Selkoe are now working with pharmaceutical companies in Canada and the Netherlands to manufacture a protollin-based nasal vaccine and move it forward toward clinical trials.
HARNESSING THE POWER OF ADULT-DERIVED STEM CELLS
Tracy Young-Pearse, PhD, a rising star with a new research lab at the center, has made tremendous progress in the use of adult-derived stem cells, which can be easily obtained from adult human tissues, to study mechanisms of brain disorders. In collaboration with center researcher Matthew J. LaVoie, PhD, she and her team have established a novel cellular model of Alzheimer’s disease, through which they can effectively study living human neurons cultured from Alzheimer’s patients. They are working to illuminate the mechanism by which the disease begins, and in collaboration with scientists at MIT, are developing a new technique for examining cell responses to new drugs that affect amyloid generation. Dr. Young-Pearse aims to apply these methodologies to other neurological diseases, further illuminating the underlying mechanisms of these diseases and opening doors to novel therapies. Dr. LaVoie is also currently using similar techniques to generate new cell models of Parkinson’s disease.
BWH Communication & Public Affairs