Discovery may be key to Alzheimer's treatment

Back to TopCommentsE-mailPrintBookmark and Share

Scientists have discovered that a gene-regulating protein that protects the developing brain of a fetus resurfaces in old age and may stave off dementia, a finding that could open a new path in Alzheimer’s research.

The research by Harvard University scientists published Tuesday in the journal Nature, showed the protein, dubbed REST, is depleted in brains of people with Alzheimer’s. It was found at a level three times higher in those who didn’t become demented even when they had brain markings of the disease. Until now, REST wasn’t known to have a role in the adult brain.

Experimental treatments, including drugs from Indianapolis-based Eli Lilly and Co., Pfizer Inc., and Johnson & Johnson, have focused on reducing proteins such as amyloid or tau that form the hallmark brain clumps of Alzheimer’s. However, they have failed to stem cognitive decline.

Since 1998, there have been more than 100 attempts to develop an Alzheimer’s drug and all failed. Lilly remains hopeful that its experimental Alzheimer’s drug can help patients in early statges of the disease.

The REST finding adds support to the idea that targeting those proteins isn’t 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 study’s lead researcher.

“There’s 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 Alzheimer’s,” though they don’t 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 brain’s 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 Yankner’s team found that the protein suppresses genes involved in cell death and Alzheimer’s progression, while turning on those that protect neurons from stress.

More than 5 million Americans have Alzheimer’s disease, the most common type of dementia, a number projected to triple by 2050, according to the Alzheimer’s 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 person’s death and could be the third-leading cause of mortality.

Protective pathways

The discovery of REST’s potential role in the aging brain highlights the need for pursuing new directions in Alzheimer’s research, said Maria Carrillo, vice president for medical and scientific relations at the Chicago-based Alzheimer’s 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 today’s findings is years away.

“Its’ a fascinating take on the concept that’s been around,” she said. “There’s not as much research in the neuroprotective aspects of aging. That is the most interesting aspect of this study and it’s important to pursue and continue research in this area.”

The Alzheimer’s 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.

Study data

In the Harvard brain-tissue tests, researchers found that the protein, mildly detectable in early adulthood, “lit up like stars,” in samples from those in their 70s to 80s, Yankner said. The study measured REST in brain samples from adults ages 20 to 35 and those ages 73 to 106.

When researchers next examined REST in brain samples from individuals with Alzheimer’s, they found the protein was almost absent from cells of the prefrontal cortex and hippocampus, regions of the brain critical for functions including memory, concentration and decision-making.

A key clue that REST protected brain cells in Alzheimer’s came from an analysis of brain tissue along with decades of test scores on memory and cognition from the Religious Orders Study and the Rush Memory and Aging Project. Researchers found that REST was significantly higher in those with Alzheimer’s brain abnormalities who didn’t develop dementia compared with those whose disease led to cognitive decline.

“Amyloid and tau may not be enough to trigger dementia,” Yankner said. “You would have to have a failure of stress response in the brain. Trying to eliminate these proteins might get you some of the distance but may not be optimally effective until you can increase the resilience of the brain to resist toxic stresses.”


Post a comment to this story

We reserve the right to remove any post that we feel is obscene, profane, vulgar, racist, sexually explicit, abusive, or hateful.
You are legally responsible for what you post and your anonymity is not guaranteed.
Posts that insult, defame, threaten, harass or abuse other readers or people mentioned in IBJ editorial content are also subject to removal. Please respect the privacy of individuals and refrain from posting personal information.
No solicitations, spamming or advertisements are allowed. Readers may post links to other informational websites that are relevant to the topic at hand, but please do not link to objectionable material.
We may remove messages that are unrelated to the topic, encourage illegal activity, use all capital letters or are unreadable.

Messages that are flagged by readers as objectionable will be reviewed and may or may not be removed. Please do not flag a post simply because you disagree with it.

Sponsored by

facebook - twitter on Facebook & Twitter

Follow on TwitterFollow IBJ on Facebook:
Follow on TwitterFollow IBJ's Tweets on these topics:
Subscribe to IBJ
  1. Good Day I am Mr (Victoria Wright) from United state of America, i stayed in NEW YORK, and i have a broke up business, until i found this company email who help me to gain a loan for business,, and now i want to used this short medium to congratulate the below company for the fast and safe money they loan to me without any form of collateral, i loan 500,000USD from the company to save my business and lots more, i saw their mail on the internet, everyone always give testimony for what they did, so i quickly contacted them and they all did everything for me without stress and my money was sent to my account just 3 days later, i was surprise and i feel so glad, now i have a standard business control agent who help me, now i will advice those who need urgent loan to contact him at the bellow email:zenithfirm12@gmail.com

  2. NOTICE:This is to inform the general public that Vampires are real. My name is James Franklyn.,am an agent of vampire,am here to introduce our new world trend to you,a world of vampire where life get easier,we have made so many persons vampires and have turned them rich,you will be assured long life and prosperity,you shall be made to be very sensitive to mental alertness,stronger and also very fast,you will not be restricted to walking at night only even at the very middle of broad day light you will be made to walk.In case you are wildly oppressed by some unscrupulous persons we can still help you fight them.Your protection is assured immediately you join.Just contact the bellow email if you are interested we are here to attend to you anytime you want us. Contact the bellow email for more details. Email:vampirescreed@hotmail.com Sincerely: James Franklyn.

  3. Bravo! Someone else that is willing to speak the truth! Bravo!_____NBCSN is available in almost 2 MILLION more homes than just a few years ago, but Indycar STILL gets less total viewers than it did just a few years ago when NBC took over Versus. Attendance and ratings cratered with the end of season races (just when the title battle got "interesting" HAH!__________And now...new race in Basilia, where Miles celebrated the "rich history" of Indycar racing there. Rich history? What, 7 events in the 100 years of AOW? Yep, some history. Well, at least its an oval. It's not??? Are you kidding me??? Gosh darn road racin furriners.

  4. PURITY RAY LOAN OFFER........ Have you been denied by your banks,or are you in need of of an urgent loan to pay of your bills we are capable of giving loans @ cheaper rate to interested individuals, student, companies and members of the public in need of finance to settle bills, we do offer considerable loans which you can count on. For more information on our various types of loan,then you will have to contact PURITY RAY LOAN FIRM, to help you achieve your desire LOAN APPLICATION FORM TO BE FILLED BORROWERS INFORMATION * Full name:………………………. * SEX * ……………………………. * Country………………………….. * State:……………………………. * Land:…………………………….. * Occupation:…………………….. * phone number:…………………. * Telephone: ………………………….. * Age:………………………………. * Amount needed as loan:……… * Loan Duration:………………….. * Propose of Loan:……………….. * Annual revenue:………………… * Monthly Income:……………….. * Guarantee:………………………. * Payment: monthly or annually Email.....purityrayloanfirm@gmail.com Thank you and God bless Mr Purity Ray PURITY RAY LOAN FIRM we tend to serve you better

  5. Problem: most of the people responding to this article don't know about this service AT ALL! Why? Lack of awareness. This isn't IndyGo. This is CIRTA: might as well be the mattress company because they are asleep at the wheel - something like 3 directors over the last year? Playing with federal grant money is great! This "region" wants commuter rail service, has spent MILLIONS on Transportation studies yet can't even support a commuter bus line? This is largely for suburban riders to get to downtown - not for "service people to work in our hotels and restaurants" ! Get your head out of your backside!! These are professionals, students etc. that don't want to fight traffic, save some money on parking, gas, stress.... if CIRTA would put their federal money into widely promoting the sevive to Greenwood, Fishers & Carmel instead of finding directors and studies - this would be a successful service. Our family uses(d) it daily for the last several years - but the recent uncertainty & now unreliability due to cuts from Carmel has been a problem. Now, costs us an additional $350/month for gas & parking ( $4200/year) plus vehicle wear, service, environmental impact ... YES - this REGION needs this this type of service in order to keep growing and getting the people it needs to fill skilled positions in downtown Indianapolis. Think outside of your own car !!!