Development of plaques and tangles in the brain lead to the characteristic Alzheimer disease symptoms of memory loss and cognitive decline.
Alzheimer’s disease is a complex disorder of the most human aspect of biology: the thinking part of the brain. Alzheimer’s disease symptoms include a gradual loss of memory and other aspects of cognitive function over the course of 10 to 20 years. These symptoms appear to be due to the insidious buildup of a protein in the brain referred to as the amyloid protein, or amyloid beta protein.
Long before a person exhibits Alzheimer’s disease symptoms, he or she will build up plaques in the brain composed of the amyloid beta protein. Shortly after the initial development of plaques, tangles also will build up in the brain. The tangles are made up of the tau protein. The plaques and tangles together mount up over decades, leading to a short-circuiting of nerve cells in the brain and the characteristic Alzheimer disease symptoms of memory loss and cognitive decline.
Since the 1980s, Dr. Dennis Selkoe, Co-Director of the Ann Romney Center for Neurologic Diseases at Brigham and Women’s Hospital (BWH), and his colleagues have been gathering data to support the Amyloid Hypothesis, in which he proposed that Alzheimer’s disease begins with the build-up of amyloid beta protein in “thinking regions” of the brain.
In 1992, Dr. Selkoe and colleagues made a surprising discovery – that the amyloid beta protein is made by everyone throughout life. This discovery raised the question – why doesn’t everyone get Alzheimer’s disease? BWH researchers found that certain genetic and environmental factors can make some people susceptible to greater amyloid buildup and the subsequent development of Alzheimer’s disease.
Currently, several pharmaceutical companies are developing treatments that use antibodies that target amyloid beta protein in the brain. Promising clinical trials of these antibodies suggest that an anti-amyloid treatment for Alzheimer’s disease may be available to patients within a few years.
Researchers also are studying whether earlier treatment with anti-amyloid antibodies and other agents may help slow or even halt the progression of Alzheimer’s disease before patients become symptomatic. The Anti-Amyloid in Asymptomatic Alzheimer’s (A4) Study is the first prevention trial for Alzheimer’s disease. The A4 Study, created and led by Dr. Reisa Sperling, Director of the BWH Center for Alzheimer Research and Treatment (CART), is currently enrolling patients at many sites in the U.S., Australia, and Canada. These still cognitively normal subjects at risk for AD will be followed over years to see whether an anti-amyloid antibody can prevent the development of Alzheimer’s disease in patients who show evidence of amyloid beta protein in their brains on a PET scan, but who are not yet experiencing Alzheimer symptoms.
In the following video, Dr. Selkoe describes progress on research to develop and characterize treatments for Alzheimer’s disease that target the amyloid beta protein: