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The Alzheimer’s Puzzle

With no cure in sight, researchers piece together strategies to keep the disease at bay

Prof. Thomas Shea in front of computer with brain on screen
Prof. Thomas Shea, above and Assoc. Prof. Garth Hall, inset below, agree that with no cure in sight, lifestyle choices may be the best way to prevent Alzheimer’s disease.

04/03/2019
By David Perry

Alzheimer’s disease is devastating to those who suffer from it and to their families, slowly and painfully robbing memories, language skills and independence from its victims. It’s also an elusive foe to the researchers trying to find a cure for the disease, which affects an estimated 5.7 million people in the United States.
With the rapidly aging population in the U.S., the number of people living with Alzheimer’s is expected to soar. By 2050, the Alzheimer’s Association projects that nearly 14 million Americans will have it.
What hope does science hold out for the millions of people who are dealing with the disease? Two Kennedy College of Sciences faculty members, Biological Sciences Prof. Thomas Shea and Assoc. Prof. Garth Hall, have devoted much of their careers to Alzheimer’s-related research, looking for possible causes and searching for ways to prevent the disease. They shared their perspectives on the latest advances in treatments and diagnosis and on the prospects for a cure.

LIVING WELL IS THE BEST REVENGE

To understand Alzheimer’s disease, it helps to understand what causes it. Shea, who has researched Alzheimer’s for more than three decades, says it’s a combination of things.
“A number of factors — genetic, environmental, nutritional and more — combine to result in the manifestation of Alzheimer’s disease. It may, in a very real way, be part of the human condition,” he says.
Shea’s research indicates that proper nutrition, mental, physical and social activity can stave off cognitive decline.
“If an individual delays cognitive decline for a protracted period, they may never experience Alzheimer’s disease,” says Shea, who compared this approach to the treatment for diabetes. “We don’t cure it, but we can manage it and, in doing so, hold back its deleterious impact. That is a ‘functional’ cure.”
Last fall, research by Shea and Framingham State University Nursing Prof. Ruth Remington found that the early stages of cognitive decline often go unnoticed. Thus, medical intervention or lifestyle changes that could hold off or even reverse the disease are delayed. Their research, which was published in the Journal of Alzheimer’s Disease, also demonstrated that lifestyle modifications are beneficial, regardless of age.
For now, living well through healthy nutrition choices and staying physically and socially active may provide the best shot for keeping the disease at bay, Shea says. “I don’t see a true cure on the horizon.”
Hall, whose chief concern is improving diagnostic approaches for Alzheimer’s, agrees that for now, lifestyle choices may be the best bet for avoiding the disease.
“There is considerable hope that improved palliative treatments will soon emerge that mitigate and delay the progression of the disease,” he says, adding that in the meantime, “staying physically and mentally active and avoiding head trauma are probably the most important general pieces of advice.”
Garth Hall in front of colorful screen
Hall’s research has focused on the role that tau proteins play in Alzheimer’s disease. He led a research team that found a new mechanism by which tau protein spreads within the brain and appears in the blood and cerebrospinal fluid of people with Alzheimer’s. The results from Hall’s research suggest that a specific kind of tau protein (tau-E2) plays a critical role in the spreading of Alzheimer’s lesions in the brain.
Hall is currently investigating the connection between Alzheimer’s and traumatic brain injury and is trying to identify “fingerprints” of proteins in body fluids that will help in diagnosing Alzheimer’s, as well as assist in triaging head injuries. He has received funding from the U.S. Army’s Telemedicine & Advanced Technology Research Center in support of his work. In collaboration with researchers from the Veterans Administration health care system and Boston University School of Medicine, he is also involved with the analysis of tissue and body fluid exosomes from retired National Football League players and people injured in explosions.
“Our work suggests that the development of ‘fingerprint’ diagnostics, based on changes in neuronal secretion that precede the onset of Alzheimer’s, is a promising approach,” he says.
Looking ahead, Shea says more work needs to be done to uncover the “initial, triggering event” that leads to Alzheimer’s. “Something occurred upstream, such as inflammation or oxidative damage, that initiates pathology that later encompasses those proteins,” he says. “There is a new line of research, with mounting evidence, that earlier viral infection may trigger part of that early inflammation.” 
Research in other areas may help the fight against Alzheimer’s. Advances in cancer treatments are likely to become relevant, and the fast-moving field of genetics may play an important role, the two researchers say.
“The more general knowledge we have about nervous system function and genetics, the more we can apply to what goes wrong in Alzheimer’s disease and other age-related disorders,” Shea says.
Shea and Hall also agree that more funding is needed. But it’s not just a matter of more money, but rather how it’s spent that could make a difference, says Hall. He expresses frustration with what he describes as Alzheimer’s research resistance to small-scale projects to test new ideas. That resistance stems partly from what he believes “is a misplaced faith in the ability of expensive, large-scale research projects” to lead to an urgently needed cure for the disease.
“Since it is clear that we have only a limited understanding of the underlying biology of Alzheimer’s disease, I think that funding could more usefully be spent in identifying and testing factors which contribute to the underlying disease mechanisms,” he says.