Featured Research

from universities, journals, and other organizations

Alzheimer’s brain protein may provide target for treating mental retardation

Date:
June 13, 2010
Source:
Rockefeller University
Summary:
From the perspective of neuroscientists, Alzheimer's disease and Down syndrome have at least one thing in common: patients with both diseases have an accumulation of -amyloid protein in their brains. Scientists now provide evidence that drugs which help reduce the level of -amyloid in the brains of Alzheimer's patients may also work to treat mental retardation in Down syndrome.

From the perspective of neuroscientists, Alzheimer's disease and Down syndrome have at least one thing in common: patients with both diseases have an accumulation of β-amyloid protein in their brains. Rockefeller University scientists now provide evidence that drugs which help reduce the level of β-amyloid in the brains of Alzheimer's patients may also work to treat mental retardation in Down syndrome.

Related Articles


The study was led by Paul Greengard, head of the Laboratory of Molecular and Cellular Neuroscience and 2000 Nobel laureate in Physiology or Medicine, and William Netzer, a research associate in Greengard's laboratory. Their research on Down syndrome grew out of the group's interest in Alzheimer's disease, which is the most common form of dementia affecting elderly populations worldwide.

"The buildup of β-amyloid is a central feature in Alzheimer's disease and also in elderly Down syndrome patients who go on to develop Alzheimer's, but it was not known whether β-amyloid contributes to mental retardation in Down syndrome children," says Greengard, Vincent Astor Professor and director of the Fisher Center for Alzheimer's Disease Research at Rockefeller. "Our study suggests that β-amyloid may be a contributing factor in mental retardation, and that gives us hope that it might be possible to improve cognitive abilities in these children."

The accumulation of β-amyloid in the brain is believed to initiate the pathological cascade leading to neuronal dysfunction, cell death and dementia. β-amyloid is derived from a protein called the amyloid precursor protein (APP) as a result of that protein's metabolism by enzymes called secretases, and β-amyloid levels are elevated in Alzheimer's disease patients as well as in both children and adults with Down syndrome. Down syndrome is a complex genetic disorder that's caused by the triplication of more than 100 genes on human chromosome 21, including the gene that encodes APP; the extra APP, scientists believe, results in extra β-amyloid.

Researchers in the Greengard laboratory were aware that nearly all individuals with Down syndrome progress to Alzheimer's dementia by the fifth or sixth decade of life. Though β-amyloid is believed to be responsible for the high prevalence of Alzheimer's in Down syndrome adults, it was not known whether elevated β-amyloid levels influence mental retardation in children with Down syndrome.

The Rockefeller scientists postulated that elevated levels of β-amyloid might influence mental retardation in children with Down syndrome, and that by lowering β-amyloid levels with drugs, cognitive ability in these children might be improved. In other words, mental retardation, which has historically been seen as an irreversible developmental defect, might in fact be treatable with drugs that lower β-amyloid.

"Our study was designed to test our hypothesis that drugs that reduce levels of β-amyloid might improve learning and memory in children with Down syndrome," says Netzer, lead author of the study, which was published in the June issue of PLoS ONE.

Using a mouse model of Down syndrome, the researchers tested a drug-like compound called DAPT, which is a secretase inhibitor known to suppress production of β-amyloid. Mice treated with DAPT not only had a rapid reduction in β-amyloid levels but also a significant improvement in their ability to learn to navigate a water maze and remember where important features were located. The behavior of normal siblings used as a control group was unaffected by DAPT.

Netzer cautions that current compounds used experimentally to lower β-amyloid generally have very toxic side effects. Several years ago, Greengard and his colleagues discovered that the anti-cancer drug Gleevec, used to treat a form of leukemia, lowered β-amyloid without the same side effects as other secretase inhibitors. Although Gleevec does not remain in the brain long enough to treat either Alzheimer's disease or Down syndrome, it may provide a model for developing new anti-amyloid drugs, says Greengard.

Karen Duff, an Alzheimer's researcher from Columbia University Medical Center, also took part in the study; behavioral tests were conducted by Craig Powell's lab at University of Texas Southwestern Medical Center.


Story Source:

The above story is based on materials provided by Rockefeller University. Note: Materials may be edited for content and length.


Journal Reference:

  1. William J. Netzer, Craig Powell, Yi Nong, Jacqueline Blundell, Lili Wong, Karen Duff, Marc Flajolet, Paul Greengard, Paul A. Adlard. Lowering β-Amyloid Levels Rescues Learning and Memory in a Down Syndrome Mouse Model. PLoS ONE, 2010; 5 (6): e10943 DOI: 10.1371/journal.pone.0010943

Cite This Page:

Rockefeller University. "Alzheimer’s brain protein may provide target for treating mental retardation." ScienceDaily. ScienceDaily, 13 June 2010. <www.sciencedaily.com/releases/2010/06/100611223124.htm>.
Rockefeller University. (2010, June 13). Alzheimer’s brain protein may provide target for treating mental retardation. ScienceDaily. Retrieved November 27, 2014 from www.sciencedaily.com/releases/2010/06/100611223124.htm
Rockefeller University. "Alzheimer’s brain protein may provide target for treating mental retardation." ScienceDaily. www.sciencedaily.com/releases/2010/06/100611223124.htm (accessed November 27, 2014).

Share This


More From ScienceDaily



More Mind & Brain News

Thursday, November 27, 2014

Featured Research

from universities, journals, and other organizations


Featured Videos

from AP, Reuters, AFP, and other news services

Are Female Bosses More Likely To Be Depressed?

Are Female Bosses More Likely To Be Depressed?

Newsy (Nov. 24, 2014) A new study links greater authority with increased depressive symptoms among women in the workplace. Video provided by Newsy
Powered by NewsLook.com
Winter Can Cause Depression — Here's How To Combat It

Winter Can Cause Depression — Here's How To Combat It

Newsy (Nov. 23, 2014) Millions of American suffer from seasonal depression every year. It can lead to adverse health effects, but there are ways to ease symptoms. Video provided by Newsy
Powered by NewsLook.com
Could Your Genes Be The Reason You're Single?

Could Your Genes Be The Reason You're Single?

Newsy (Nov. 21, 2014) Researchers in Beijing discovered a gene called 5-HTA1, and carriers are reportedly 20 percent more likely to be single. Video provided by Newsy
Powered by NewsLook.com
Milestone Birthdays Can Bring Existential Crisis, Study Says

Milestone Birthdays Can Bring Existential Crisis, Study Says

Newsy (Nov. 21, 2014) Researchers find that as people approach new decades in their lives they make bigger life decisions. Video provided by Newsy
Powered by NewsLook.com

Search ScienceDaily

Number of stories in archives: 140,361

Find with keyword(s):
Enter a keyword or phrase to search ScienceDaily for related topics and research stories.

Save/Print:
Share:

Breaking News:

Strange & Offbeat Stories


Health & Medicine

Mind & Brain

Living & Well

In Other News

... from NewsDaily.com

Science News

Health News

Environment News

Technology News



Save/Print:
Share:

Free Subscriptions


Get the latest science news with ScienceDaily's free email newsletters, updated daily and weekly. Or view hourly updated newsfeeds in your RSS reader:

Get Social & Mobile


Keep up to date with the latest news from ScienceDaily via social networks and mobile apps:

Have Feedback?


Tell us what you think of ScienceDaily -- we welcome both positive and negative comments. Have any problems using the site? Questions?
Mobile: iPhone Android Web
Follow: Facebook Twitter Google+
Subscribe: RSS Feeds Email Newsletters
Latest Headlines Health & Medicine Mind & Brain Space & Time Matter & Energy Computers & Math Plants & Animals Earth & Climate Fossils & Ruins