Scientists have discovered that a gene-regulating protein that guards the developing brain of a fetus reboots in old age and may protect against dementia, a finding that could open a new path in Alzheimers research.

The research by Harvard University scientists published today in the journal Nature, showed the protein, dubbed REST, is depleted in brains of people with Alzheimers. It was found at a level three times higher in those who didnt become demented even when they had brain markings of the disease. Until now, REST wasnt known to have a role in the adult brain.

Experimental drugs to reduce proteins such as amyloid or tau that form the hallmark brain clumps of Alzheimers have failed to stem cognitive decline. Todays finding adds support to the idea that targeting those proteins isnt enough fight the disease. It also may explain why some people develop dementia as they age while others live long lives, lucid into their 90s or 100s, said Bruce Yankner, the studys lead researcher.

Theres a longstanding puzzle in neurology why a large percentage of the aging population when they die have enough abnormalities in the brain to classify as Alzheimers, though they dont develop the dementia, said Yankner, a professor of genetics at Harvard Medical School in Boston. In addition to trying to remove toxic proteins, which many clinical trials do with limited success, we may need to augment the brains natural defense.

Until now, the REST protein was thought to be active only in fetal development and switched off in the brain after birth. A series of experiments by Yankners team found that the protein suppresses genes involved in cell death and Alzheimers progression, while turning on those that protect neurons from stress.

More than 5 million Americans have Alzheimers disease, the most common type of dementia, a number projected to triple by 2050, according to the Alzheimers Association. The disease is the sixth-leading cause of death in the U.S., according to the Centers for Disease Control and Prevention. A March 6 study published in Neurology found the disease may be under-reported as a reason for a persons death and could be the third-leading cause of mortality.

Experimental treatments, including drugs from Pfizer Inc., Johnson & Johnson and Eli Lilly & Co. that have focused on reducing amyloid havent slowed the debilitating loss of mental functioning that characterizes Alzheimers. Since 1998, there have been more than 100 attempts to develop an Alzheimers drug and all failed.

The discovery of RESTs potential role in the aging brain highlights the need for pursuing new directions in Alzheimers research, said Maria Carrillo, vice president for medical and scientific relations at the Chicago-based Alzheimers Association. The idea that the brain may harbor pathways, such as REST, to protect against cognitive decline is one of them. Still, any potential drug based on the todays findings is years away.

Its a fascinating take on the concept thats been around, she said. Theres not as much research in the neuroprotective aspects of aging. That is the most interesting aspect of this study and its important to pursue and continue research in this area.

The Alzheimers Association is a sponsor of a clinical trial, called LEARN, designed to look at individual variation in disease progression. One objective of LEARN is to find causes of cognitive decline besides amyloid buildup.

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Fetal-Brain Protein Sparks in Old Age to Fight Dementia

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