The protein that may decide whether you get Alzheimer's

Study links REST levels to symptoms of dementia

Researchers have identified a protein in the brain that may explain why some individuals are more vulnerable to Alzheimer's disease than others.

Alzheimer's hits women much harder than men

The research, published on Wednesday in the journal Nature, pinpoints a protein called REST, which acts as a regulator that disables certain genes.

A landmark finding

REST was primarily thought to only be active during fetal brain development, says study author Bruce Yankner, a professor of genetics at Harvard Medical School. But while investigating age-related changes in the brain, researchers were surprised to find that REST was also the most active gene regulator in older brains.

Yankner hypothesized that REST reactivates later in life in response to stress. The protein appears to switch off genes that promote cell death, protecting neurons from normal aging processes like energy decrease, inflammation, and oxidative stress.

Data from brain banks and dementia studies confirmed that brains of young adults ages 20 to 35 contained little REST, while healthy adults between the ages of 73 and 106 had high levels of the protein, with the levels increasing with age.

Meanwhile, the brains of older individuals with Alzheimer's, mild cognitive impairment, and dementia contained much less REST than healthy brains. A person with Alzheimer's disease who had yet to decline cognitively had three times more REST than people who were symptomatic. As a person's symptoms worsened, REST levels declined in certain areas of the brain, including the prefrontal cortex and hippocampus—areas critical to learning, memory, and planning, the study found.

Why levels vary

Yankner says that REST appears to work by traveling to a neuron's nucleus when the brain is under stress. However, in a person with dementia, REST somehow gets diverted, moving with toxic dementia-related proteins to another part of the neuron, where it is eventually eliminated.

"Our work raises the possibility that the abnormal protein aggregates associated with Alzheimer's and other neurodegenerative diseases may not be sufficient to cause dementia; you may also need a failure of the brain's stress response system," Yankner said, adding that if the findings are confirmed, "this opens up a new area in terms of treatment possibilities."

However, experts say the research leaves many unanswered questions. Bradley Wise of the National Institute on Aging says REST's role in the neurocognitive disease is still unclear. "I don't think you can really say if it's a cause of Alzheimer's or a consequence of Alzheimer's," he says.

Samuel Gandy, an Alzheimer's researcher at Mount Sinai Medical Center, also questioned REST's role in other cognitive disorders, which could make it more difficult to create related treatments. He explained, "My ambivalence is, is this really a way that advances our understanding of the disease or does this just tell us this is even more complicated than we thought?" (Belluck, New York Times, 3/19; Emling, Huffington Post, 3/19).

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