Protein REST sheds some light on aging and Alzheimer s disease

By ACSH Staff — Mar 20, 2014
About 7 million Americans have Alzheimer s disease today, burdening families with not only the added role of providing care

Screen Shot 2014-01-24 at 1.10.31 PMAbout 7 million Americans have Alzheimer s disease today, burdening families with not only the added role of providing care for their loved ones, but also with the frustration of having a very limited understanding of the cause (or causes) of the disease. Scientists and medical researchers have thus far associated the brain disease with a buildup of plaques and nerve-fiber tangles (only detected on post-mortem exams) in certain cortical areas. However, these have not upheld as necessary and sufficient indicators of the disease. The NYTimes reported on a new study published this Wednesday in Nature, that might provide some potential for elucidating the underpinnings of this complex brain disease.

The study describes a malfunction in the brain s stress response system, which may leave individuals more susceptible to developing Alzheimer s disease. When researchers were studying changes in the genetic landscape as people age, they found the protein REST as the most active gene regulator in older brains. Lead author of the study, Dr. Bruce A. Yankner, defines the protein as, ¦a regulator that switches off certain genes ¦primarily known to keep fetal neurons in an immature state until they develop to perform brain functions.

The Harvard team probed the activity of REST, initially analyzing post-mortem brains, followed by laboratory research in mice, roundworms, and cells. Dr. Yankner noted that by the time babies are born, REST becomes inactive, except in some areas outside the brain like the colon, where it seems to suppress cancer. The team of scientists wrestled with why the fetal gene would become active later in life with increasing age. Supporting their hypothesis, the results of the studies showed that REST appears to switch off genes that promote cell death, protecting neurons from normal aging processes like energy decrease, inflammation and oxidative stress. In essence, REST operates as an endogenous defense system as healthy individuals age.

Indeed, post-mortem analysis confirmed the importance of REST in aging people, implying that it may be related to longevity. Researchers studied brains from brain banks and dementia studies, finding that brains of young adults ages 20 to 35 contained little REST, while healthy adults between the ages of 73 and 106 had plenty. In addition, in people with Alzheimer s, mild cognitive impairment, [and other forms of diminished cognitive function], the brain areas affected...contained much less REST than healthy brains. The levels of REST decreased in correlation with the severity of cognitive decline, and only in key brain areas: the prefrontal cortex and hippocampus, both areas central to learning, memory and planning. Moreover, areas not associated with Alzheimer displayed no changes in REST.

To account for shortcomings of post-mortem analysis, the researchers also carried out laboratory investigation. Particularly promising were data in which mice genetically engineered to lack REST lost neurons as they aged in brain areas affected in Alzheimer s.

Though these findings illuminate more details linked to Alzheimer s disease, experts are unclear what to make of all of it, because there is no conclusive evidence as to whether REST is a cause or an effect of the disease. In addition, further investigation of REST must address whether its activity is Alzheimer s-specific or also involved in other brain disorders. Researchers in the field add that if the former is true, perhaps REST maybe the target of new and novel therapy.

Overall, the study very well done, and certainly helps support this idea that we ve all tried to understand about why Alzheimer s is age-associated and why, while amyloid is necessary for the development of Alzheimer s disease, it certainly is not sufficient, says Dr. John Morris, an Alzheimer s researcher from Washington University in St. Louis. However, at present, we must appreciate this new clue and remain persistent in studying different causes of the disease because as Dr. Morris stated, There have to be some other processes and triggers that result in Alzheimer s.

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