Lay the scientific foundation for novel approaches to treat Alzheimer’s disease

Dr. Yankner’s research into the aging process has significant clinical ramifications because many diseases are associated with advanced age. However, the molecular basis of normal aging, as well as its relationship to neurodegenerative diseases, is poorly understood. Dr. Yankner brings a wealth of scientific and clinical experience to this important area of study. The urgent need for new therapeutics is clear: the United States population demographics indicate a significant increase in citizens who are 65 years of age or older. By 2050, this population segment will represent 21% of the population (86 million people), an increase from the current 12%. It is estimated that 50% of senior citizens over the age of 85 have dementia, mostly due to Alzheimer’s disease.

Most of the current research efforts in Alzheimer’s disease are focused on the disease itself, and so far, clinical trials of new therapeutics have not fared well. By probing the basic molecular circuitry in brain cells that changes as people age, and by comparing healthy circuitry to the disease state, Dr. Yankner is poised to develop paradigm-shifting approaches for this disease.

Dr. Yankner is investigating the molecular biology of the normal aging process and how it goes awry in Alzheimer’s and other neurological diseases. His research goal is to improve the detection, prognosis, and treatment of age-related cognitive disorders. The lab employs global molecular profiling technologies, bioinformatics, mouse models, and human samples, to elucidate key aspects of gene expression in mouse and primate brain neuronal cells that underlie the aging process.

Bruce A. Yankner, M.D., Ph.D., is Professor of Pathology and Neurology at Harvard Medical School, Director of the Harvard Neurodegeneration Training Program, and Co-Director of the Paul F. Glenn Laboratories for Biological Mechanisms of Aging. Dr. Yankner graduated from Princeton University, received his M.D. and Ph.D. from Stanford University, and did a residency at Massachusetts General Hospital. His work has contributed to understanding pathogenic mechanisms in Alzheimer's disease, Down’s syndrome and Parkinson’s disease, beginning with the initial observation that amyloid beta protein is a toxic molecule, and later with investigations into the roles of presenilin proteins, notch and wnt in neuronal signaling and pathology. Recent work from his laboratory has defined the transcriptome of the aging human brain, its evolution from mouse to man, and a potential role for DNA damage in age-related cognitive changes and pathology. He has received the Major Award for Medical Research from the Metropolitan Life Foundation, the Derek Denny-Brown Neurological Scholar Award from the American Neurological Association, the Irving S. Cooper Award from the Mayo Clinic, the Ellison Medical Foundation Senior Scholar Award, and the 2009 Nathan W. Shock award for aging research from the National Institute on Aging.

A recent study from Dr. Yankner’s lab revealed striking data on age-related changes in primate brain gene expression. Dr. Yankner’s genome-wide analysis of mRNA and protein expression discovered  that the expression of a number of neuronal genes are depressed, including genes that promote synaptic function. These findings suggest a molecular scenario that links the aging process with a decline in cognitive function, and sheds light on potential pathological mechanisms that underlie the development of neurodegenerative diseases.

A separate study investigated the etiology of amyloid deposits, which are a hallmark of Alzheimer’s disease. Intriguingly, experimental data established that sub-physiological levels of calcium could promote the formation of amyloid fibrils, which are toxic to neurons. These data establish an important link between calcium and amyloid plaques, and might facilitate novel approaches for treating Alzheimer’s disease.  

Biological Mechanisms and Pathways

• Aging •
• Amyloid precursor protein •
• DNA damage •
• Evolution •
• Gene regulation •
• Neural network •
• Population demographic •
• Systems Biology •
• Transcription
•  

Central Nervous System

• Amyloid plaque •
• Amyloid precursor protein •
• Amyloid precursor protein (APP) •
• Cognition •
• Neural network •
• Neurodegenerative disease •
• Parkinson’s disease •
• Presenilin
•  

Diagnostics

• Disease prognosis
•  

Disease Mechanisms

• Alzheimer’s disease •
• Amyloid plaque •
• Amyloid precursor protein (APP) •
• Disease prognosis •
• Neurodegenerative disease •
• Parkinson’s disease •
• Presenilin
•  

Metabolism; Metabolic Disease and Aging

• Aging
•  

Research Tools and Instrumentation

• Global molecular profiling •
• Mouse models
•  

Therapeutic Discovery Tools and Assays

• Mouse models
•  

Therapeutics

• Disease prognosis
•