MetLife Foundation today announced the recipients of its 2013 Awards for Medical Research in Alzheimer's Disease: Yueming Li, Ph.D., member and professor, Sloan-Kettering Institute and director and professor, Graduate Program in Pharmacology, Weill Medical College of Cornell University, and Lennart Mucke, M.D., director, Gladstone Institute of Neurological Disease, Joseph B. Martin Distinguished Professor of Neuroscience and professor of Neurology, University of California, San Francisco (UCSF).
Dr. Li has shown how an enzyme known as gamma-secretase functions to produce amyloid-beta, a protein that accumulates as "plaques" in the brains of those with Alzheimer's disease, damaging their neurons and connections. He has also developed a novel way to study the gamma-secretase complex, which is now enabling his lab and others to screen for potential treatments.
Dr. Mucke has identified molecular and cellular processes by which small assemblies of amyloid-beta impair cognitive functions. He demonstrated that these assemblies cooperate with tau, another protein that accumulates in Alzheimer brains, in disrupting the activity of brain networks. He also showed that suppressing the abnormal excitability of these networks can reverse cognitive and behavioral deficits in animal models of Alzheimer's disease.
The winners were recognized at a scientific briefing and awards ceremony today in New York.
"MetLife Foundation is proud to present our awards to these outstanding researchers, whose work helps bring us closer to finding a cure for Alzheimer's disease," said Dennis White, president and chief executive officer, MetLife Foundation. "Doctors Li and Mucke have made significant contributions that have also enabled other scientists to explore promising new avenues of Alzheimer's disease treatment."
About the Awards
Now in their 27th year, the awards provide outstanding researchers with an opportunity to freely pursue new ideas. At the heart of the program is a belief in research as the road to understanding and ultimately treating this devastating disease. Each major award recipient receives a $200,000 research grant for his or her institution to further their work, and a personal prize of $50,000. MetLife Foundation established the awards in 1986 to recognize and reward scientists demonstrating significant contributions to the understanding of Alzheimer's disease.
The MetLife Awards for Medical Research in Alzheimer's Disease are managed by the American Federation for Aging Research (AFAR). Founded in 1981, AFAR has championed the cause and supported the funding of science in healthier aging and age-related medicine.
"We have selected these individuals because their work has provided major insights to the field and is likely to lead to new Alzheimer's disease treatments, which are desperately needed," said David M. Holtzman, M.D., chair of the MetLife Awards for Research in Alzheimer's Disease Advisory Committee, which selected the winners. Dr. Holtzman, who is Andrew B. and Gretchen P. Jones Professor and chairman, Department of Neurology, Washington University School of Medicine, is a previous recipient of the MetLife Foundation Award.
According to recent estimates, without the development of treatments that either delay its onset or slow its progression, by 2050 well over 100 million and possibly as many as 200 million people worldwide will be living with Alzheimer's disease. The time spent caring for people with Alzheimer's disease will be measured in billions of hours, and the cost will be trillions of dollars.
Seminal Discoveries That Have Taken Alzheimer's Research in New Directions
Drs. Li and Mucke have made significant, ongoing discoveries that have identified underlying mechanisms of Alzheimer's disease and led to promising new directions for treatment.
Dr. Li, who is a lab head in the Molecular Pharmacology and Chemistry Program at Memorial Sloan-Kettering Cancer Center, has made a number of seminal discoveries about the enzyme gamma-secretase and its role in the pathology of Alzheimer's disease. In a 2000 publication in Nature, his team provided the first compelling biochemical evidence that gamma-secretase activity is triggered by subunits within this complex called presenilin. Presenilins, when mutated, can lead to Alzheimer's disease.
In 2010, his lab reconstituted gamma-secretase and provided proof that presenilin contains the active site for gamma-secretase. This finding provided a unique platform for further study, which is now being done by a number of research teams, of the structure and function of gamma-secretase at both the molecular and atomic levels. Dr. Li's discovery provides further proof that gamma-secretase is a potential target for the development of Alzheimer's treatments.
Dr. Li's primary research focus is now on modulating gamma-secretase activity in order to change the processing of amyloid precursor protein (APP), a protein implicated in the development of Alzheimer's disease, and translating this knowledge into targeted therapies.
As director of the Gladstone Institute of Neurological Disease, Dr. Mucke and his team have made a number of significant discoveries on the mechanisms underlying Alzheimer's disease, and have identified novel therapeutic strategies for blocking these mechanisms. His lab showed that the activities of the proteins amyloid-beta, apoE4 and tau, all of which are known to be involved in Alzheimer's disease, can disturb communication among brain cells. Dr. Mucke's team also discovered that the interactions of these proteins play an early role in disrupting the brain's neural networks. In addition, Dr. Mucke found that some of the over-excitation of neurons known to be an early characteristic of Alzheimer's disease results from the combined actions of amyloid-beta and tau.
These results led Dr. Mucke to initiate experiments to determine whether blocking abnormal network activity could be a potential therapeutic strategy. This has proven to be an area of great promise in drug discovery.
Dr. Mucke's current emphasis is on the role of DNA damage and aging-related factors in cognition, and on turning his lab's latest findings into potential treatments.
For additional background on the award recipients, visit: http://www.afar.org/research/MLF-awards
About MetLife Foundation
MetLife Foundation was established in 1976 by MetLife to carry on its long tradition of corporate contributions and community involvement. For over 25 years, MetLife and MetLife Foundation have invested more than $20 million for Alzheimer's research and public information programs, including over $13 million through the Awards for Medical Research in Alzheimer's Disease program. The Foundation has also supported a number of major initiatives, including the PBS documentary The Forgetting: A Portrait of Alzheimer's; short pocket films on Alzheimer's narrated by David Hyde-Pierce; an educational initiative with the National Institute on Aging's Alzheimer's Disease Centers; the film Alzheimer's Disease: Facing the Facts; and initiatives that include caregiving videos, Alzheimer's toolkits and resources for the Hispanic community.