Emory researchers offer a new perspective on the mechanism behind Alzheimer’s disease

New findings from Emory University challenge existing theories about the origins of Alzheimer’s disease, the leading cause of dementia in older adults worldwide. A team led by researchers at the Goizueta Brain Health Institute has found strong evidence supporting a new understanding of the mechanism behind Alzheimer’s disease.

In an article published on August 9 in Cell reports medicineTodd E. Golde and Yona Levites explain how the deposits of amyloid beta, long known to accumulate in the brains of Alzheimer’s patients, serve as a kind of scaffolding for the accumulation of other proteins. Because many of these proteins have known signaling functions, their presence around the amyloid buildups known as plaques could be the culprit causing brain cell damage rather than the amyloid itself.

In the brains of people suffering from Alzheimer’s disease, amyloids build up and form a sticky plaque that disrupts brain function and causes cognitive decline. The big unknown is how exactly that happens. According to the most widely accepted hypothesis, the buildup of amyloid beta disrupts cell-to-cell communication and activates immune cells in a process that ultimately destroys brain cells.

In the study, Golde, director of the Emory Center for Neurodegenerative Disease at the Goizueta Institute, Levites, associate professor at Emory University’s School of Medicine, and their colleagues presented a new hypothesis, highlighting a different role for amyloid beta, a simple protein that forms in all brains but normally dissolves through natural processes. In experiments, they used advanced analytical technologies to identify and measure the levels of more than 8,000 proteins in human brains with Alzheimer’s disease, as well as similar proteins in mice. By focusing on proteins whose levels rose most dramatically, they identified more than twenty proteins that accumulate along with amyloid beta in both the human brains with Alzheimer’s disease and those of mice. As the investigation continues, they suspect they will find even more.

Once we identified these new proteins, we wanted to know if they were just markers of Alzheimer’s disease or if they could actually change the fatal pathology of the disease. To answer that, we focused on two proteins, midkine and pleiotrophin. Our research showed that they accelerated amyloid aggregation, both in the test tube and in mice. In other words, these extra proteins may play an important role in the process that leads to brain damage, rather than the amyloid itself. This suggests they could provide a basis for new therapies for this devastating brain disorder that has proven frustratingly resistant to treatment over the years.”

Todd E. Golde, director, Emory Center for Neurodegenerative Disease at the Goizueta Institute, Levites, associate professor, Emory University’s School of Medicine

Although the basic principles of Alzheimer’s disease have been known for more than a century, the search for a cure has been slow, often marked by repeated cycles of initially promising treatments that failed in trials, and by ongoing controversies over competing theories to achieve the best results. to reach. Explain how the disease damages the brain. As the researchers put it, “The initial idea of ​​a purely linear amyloid cascade is now recognized as simplistic. Studies have revealed the enormous complexity of changes that occur over decades in the brains of individuals as the pathologies of Alzheimer’s emerge.”

Significantly, in addition to amyloid beta, multiple forms of amyloid accumulation are involved in more than thirty human conditions that affect tissues and organs throughout the body. Because this new research proposes a new process by which Alzheimer’s disease develops, it may enable new approaches to discover treatment targets for other diseases as well.