October 20, 2022 – Alzheimer’s disease is one of the world’s largest public health problems, affecting an estimated 55 million people worldwide. Yet for decades, doctors and scientists have struggled to understand the degenerative brain disease and develop effective treatments.
At the 25th annual John B. Little (JBL) Symposium, held virtually at Harvard T.H. Chan School of Public Health on October 14, experts discussed some of the latest research on Alzheimer’s causes and potential treatments.
“While our understanding of this disease continues to advance, its causes are not completely understood, and effective measures for treatment and prevention remain elusive,” said Dean Michelle Williams in opening remarks.
The symposium, organized each year by the John B. Little Center for Radiation Sciences, is named for former professor Little, who passed away two years ago. JBL Center faculty who spoke at the event included symposium organizer Zachary Nagel, assistant professor of radiation biology; Marc Weisskopf, Cecil K. and Philip Drinker Professor of Environmental Epidemiology and Physiology; and Kristopher Sarosiek, assistant professor of radiation biology.
Weisskopf noted that dementia was the seventh leading cause of death in the U.S. in 2020—a year in which COVID-19 was third. In 2019, the estimated global cost of caring for those with dementia was $1.3 trillion. Alzheimer’s, he continued, is the primary form of dementia, and studies show while there is a clear genetic component to the disease, it is also brought on by environmental and behavioral factors, including depression, social isolation, and physical inactivity. From a public health perspective, “it raises this exciting idea that there are perhaps things we can do to reduce the burden of Alzheimer’s,” Weisskopf said. “Even delaying the onset of Alzheimer’s by a few years can have a tremendous impact socially and financially.”
Dennis Selkoe, Vincent and Stella Coates Professor of Neurologic Diseases at Harvard Medical School and Brigham and Women’s Hospital, detailed his research into beta-amyloid and tau proteins, which can build up to create tangles in brain synapses. While acknowledging that the exact association between these proteins and degenerative diseases such as Alzheimer’s is not completely known, Selkoe presented evidence showing that blocking their aggregation can help slow cognitive decline.
He further discussed the recent failures of the drug aducanumab, a monoclonal antibody treatment developed by Biogen, that decreased beta-amyloid proteins but failed to provide adequate cognitive benefits in clinical trials. In results released last month, however, another drug, lecanemab, developed by Biogen and Eisai, decreased both proteins and cognitive decline. Many hospitals, Selkoe said, are actively preparing to administer lecanemab if it receives FDA approval.
Keenan Walker, a researcher with the Laboratory of Behavioral Neurosciences at the National Institutes of Health (NIH), detailed his research into some 5,000 proteins in a longitudinal study, finding several dozen in patients in middle age that seem to be important biomarkers for developing Alzheimer’s later in life. Wilhelm Bohr, a researcher with the NIH’s Laboratory of Molecular Gerontology, described his work investigating DNA damage, which can lead to mitochondrial dysfunction also associated with the disease. His work suggests that methods of DNA repair may be able to help to limit Alzheimer’s onset.
Finally, Melinda Power of George Washington University explained her research into the connections between air pollution and Alzheimer’s, detailing several studies showing higher rates of the disease among people living in areas with higher levels of toxic particulates. While cautioning that data is not yet conclusive, she said the research holds promise for shedding light on how to decrease the incidence of Alzheimer’s. “Efforts to identify and intervene on these modifiable risk factors [related to air pollution],” she said, “are exciting because you can modify them without requiring individual-level behavior change.”