It is one of the big scientific mysteries of Alzheimer’s disease: Why do some people whose brains accumulate the plaques and tangles so strongly associated with Alzheimer’s not develop the disease?
Now, a series of experiments by Harvard scientists suggests a possible answer – one that could lead to new treatments if confirmed by other research.
The memory and thinking problems of Alzheimer’s disease and other dementias, which affect an estimated 7 million Americans, may be related to a failure in the brain’s stress response system, the new research suggests. If this system is working well, it can protect the brain from abnormal Alzheimer’s proteins; if it gets derailed, key areas of the brain start degenerating.
“This is the first study that is really starting to provide a plausible pathway to explain why some people are more vulnerable to Alzheimer’s than other people,” said Li-Huei Tsai, director of the Picower Institute for Learning and Memory at the Massachusetts Institute of Technology, who was not involved in the research but wrote a commentary accompanying the study.
The research, published in the journal Nature, focuses on a protein previously thought to act mostly in the brains of developing fetuses. The scientists found the protein also appears to protect neurons in healthy older people from aging-related stresses. But in people with Alzheimer’s and other dementias, the protein is sharply depleted in key brain regions.
Experts said if other scientists could replicate and expand upon the findings, the role of the protein, called REST, could spur development of new drugs for dementia, which has so far been virtually impossible to treat.
While investigating how different genes in the brain change as people age, Dr. Bruce A. Yankner, a professor of genetics at Harvard Medical School and the lead author of the new study, and his team were startled to find REST was the most active gene regulator in older brains. REST appears to switch off genes promoting cell death, protecting neurons from normal aging processes, like energy decrease and inflammation.
