At a AAAS Lecture, Harvard Dr. Dennis Selkoe Details Progress on Alzheimer's

An acceleration of the scientific assault on Alzheimer's disease has recently led to human trials of agents that might actually slow the disease, including a novel "vaccine" approach. If such approaches prove successful, they may offer insights into the treatment of Parkinson's Huntington's and other neurodegenerative diseases, a top researcher said in a lecture at AAAS in Washington.

At a public lecture, Dr. Dennis J. Selkoe of Harvard Medical School and Brigham and Women's Hospital noted that there are several current possibilities for treating Alzheimer's, but the most intriguing may be one in which a "vaccination" would prevent the aggregation of a protein that leads to the synaptic failure in the brain that is a hallmark of the disease. Clinical trials are only beginning to address this possible mode of treatment, Selkoe cautioned, and there is much research ahead, but it offers a hopeful new course for addressing the devastating disease that affects many millions worldwide.

"The main message today is that we begin to see an opening, a window, to a treatment for Alzheimer's disease that might actually slow or ultimately prevent the disorder," Selkoe said. "If that turns out to be true, well, then, that's going to change things a lot for our population, and not just our population, of course, but populations around the world. If we can envision being rewarded for our longevity, not by having our minds taken away from us, but rather by continuing to be alert and interactive and using our faculties of language and judgment and memory—wouldn't that be remarkable?"

The effects of Alzheimer's can be seen in some 3-4 million Americans and more than 15-20 million persons worldwide. It is estimated this number in the U.S. may increase to around 9-10 million by 2050. As Alzheimer's moves insidiously through the stages of its development, one experiences a progressive loss of memory, disorientation to date, time, and place, decreased functioning in everyday tasks, and loss of emotional stability, language and even motor control.

The financial costs, too, are staggering: Medicare expenditures for treating the disease were $31.9 billion in 2000, and could approach $50 billion by 2010. Yet Medicare represents only a small portion of the total expense for Alzheimer's disease, financing less than a quarter of the cost. The rest comes from the pockets of the victims and their families and from their employers.

Public interest in the disease has been heightened since this summer, with the death of former President Ronald Reagan, who suffered from Alzheimer's.

While research seeks to address the medical needs of the affected population, David Hogue of Garrett Evangelical Theological Seminary in Evanston, Ill., said at the lecture that study of the disease has also shown that Alzheimer's "has laid bare some of the most painful vulnerabilities of human existence we've had to encounter."

As the respondent to Selkoe's lecture, Hogue spoke of his gratefulness for the research being conducted by Selkoe and other scientists and focused on the need to care for this most vulnerable population. Viewing Alzheimer's gives us insights into our perception of being human, Hogue said. Namely, to be human is associated with our capacity to create stories about ourselves—and to remember those stories. Hogue quoted neuroscientist Joseph LeDoux, "Without a story, a person has no soul," and pastoral theologian James Ashbrook, "We are our memories, and without them, we are nothing."

James Miller, senior program associate for AAAS's Dialogue on Science, Ethics and Religion and an organizer of the event, noted that research like Selkoe's may ultimately reveal the underlying mechanisms of Alzheimer's and thereby lead to new therapies or preventive measures. "This research is also providing insights into the neurological processes that help constitute the human person or subject," Miller said after the lecture. "These insights are consistent with particular ancient religious intuitions that a human being is a psychosomatic unity rather than an enfleshed mind or spirit, as some forms of classical and modern philosophy have held."

Selkoe echoed the ideas expressed by Hogue and Miller. Alzheimer's "attacks that which makes us most human, robbing us of our precious qualities of mind and personality," he said. "The great irony here may be that while modern medicine has allowed us to live longer, it has also allowed us to suffer this disease in our later days."

Selkoe, the Vincent and Stella Coates Professor of Neurologic Diseases at Harvard Medical School and director of the Center for Neurologic Diseases at Brigham and Women's Hospital, has spent the majority of his career advancing Alzheimer's research. In 1982, he developed a method for isolating the abnormal "neurofibrillary tangles" in the brain that are a sign of Alzheimer's and developed the first antibodies to them. He continued his research on the "amyloid beta" proteins (Aß) found in the brains' of Alzheimer's patients, and has since learned much about which proteases are responsible for the abnormalities found in these protein deposits. His current research is focused on continuing to identify specific targets for drugs that could lower the abnormal Aß levels in order to prevent Alzheimer's and related diseases.

The AAAS's Dialogue on Science, Ethics and Religion lecture program was developed by AAAS to facilitate discussion among religious and ethical groups and scientists in a public forum. More information about the program and future lectures may be obtained at www.aaas.org/spp/dser.

— Jessica Lawrence-Hurt

29 September 2004