Featured Research

from universities, journals, and other organizations

Drug reverses Alzheimer's disease deficits in mice

Date:
May 23, 2013
Source:
University of Pittsburgh Schools of the Health Sciences
Summary:
An anti-cancer drug reverses memory deficits in an Alzheimer's disease mouse model, new research shows. The article reviewed previously published findings on the drug bexarotene, approved by the US Food and Drug Administration for use in cutaneous T cell lymphoma.

In new research, scientists confirm that an anti-cancer drug reverses memory deficits in an Alzheimer's disease mouse model.
Credit: fergregory / Fotolia

An anti-cancer drug reverses memory deficits in an Alzheimer's disease mouse model, University of Pittsburgh Graduate School of Public Health researchers confirm in the journal Science.

Related Articles


The research, funded by the National Institutes of Health's National Institute on Aging and Alzheimer's Association, reviewed previously published findings on the drug bexarotene, approved by the U.S. Food and Drug Administration for use in cutaneous T cell lymphoma. The Pitt Public Health researchers were able to verify that the drug does significantly improve cognitive deficits in mice expressing gene mutations linked to human Alzheimer's disease, but could not confirm the effect on amyloid plaques.

"We believe these findings make a solid case for continued exploration of bexarotene as a therapeutic treatment for Alzheimer's disease," said senior author Rada Koldamova, M.D., Ph.D., associate professor in Pitt Public Health's Department of Environmental and Occupational Health.

Dr. Koldamova and her colleagues were studying mice expressing human Apolipoprotein E4 (APOE4), the only established genetic risk factor for late-onset Alzheimer's disease, or APOE3, which is known not to increase the risk for Alzheimer's disease, when a Case Western Reserve University study was published last year stating that bexarotene improved memory and rapidly cleared amyloid plaques from the brains of Alzheimer's model mice expressing mouse Apolipoprotein E (APOE). Amyloid plaques consist of toxic protein fragments called amyloid beta that seem to damage neurons in the brain and are believed to cause the associated memory deficits of Alzheimer's disease and, eventually, death.

Bexarotene is a compound chemically related to vitamin A that activates Retinoic X Receptors (RXR) found everywhere in the body, including neurons and other brain cells. Once activated, the receptors bind to DNA and regulate the expression of genes that control a variety of biological processes. Increased levels of APOE are one consequence of RXR activation by bexarotene. The Pitt researchers began studying similar compounds a decade ago.

"We were already set up to repeat the Case Western Reserve University study to see if we could independently arrive at the same findings," said co-author Iliya Lefterov, M.D., Ph.D., associate professor in Pitt Public Health's Department of Environmental and Occupational Health. "While we were able to verify that the mice quickly regained their lost cognitive skills and confirmed the decrease in amyloid beta peptides in the interstitial fluid that surrounds brain cells, we did not find any evidence that the drug cleared the plaques from their brains."

The Pitt researchers postulate that the drug works through a different biological process, perhaps by reducing soluble oligomers which, like the plaques, are composed of the toxic amyloid beta protein fragments. However, the oligomers are composed of smaller amounts of amyloid beta and, unlike the plaques, are still able to "move."

"We did find a significant decrease in soluble oligomers," said Dr. Koldamova. "It is possible that the oligomers are more dangerous than the plaques in people with Alzheimer's disease. It also is possible that the improvement of cognitive skills in mice treated with bexarotene is unrelated to amyloid beta and the drug works through a completely different, unknown mechanism."

In the Pitt experiments, mice with the Alzheimer's gene mutations expressing human APOE3 or APOE4 were able to perform as well in cognitive tests as their non-Alzheimer's counterparts 10 days after beginning treatment with bexarotene. These tests included a spatial test using cues to find a hidden platform in a water maze and a long-term memory test of the mouse's ability to discriminate two familiar objects following introduction of a third, novel object.

Bexarotene treatment did not affect the weight or general behavior of the mice. The drug was equally effective in male and female mice.


Story Source:

The above story is based on materials provided by University of Pittsburgh Schools of the Health Sciences. Note: Materials may be edited for content and length.


Cite This Page:

University of Pittsburgh Schools of the Health Sciences. "Drug reverses Alzheimer's disease deficits in mice." ScienceDaily. ScienceDaily, 23 May 2013. <www.sciencedaily.com/releases/2013/05/130523143541.htm>.
University of Pittsburgh Schools of the Health Sciences. (2013, May 23). Drug reverses Alzheimer's disease deficits in mice. ScienceDaily. Retrieved November 22, 2014 from www.sciencedaily.com/releases/2013/05/130523143541.htm
University of Pittsburgh Schools of the Health Sciences. "Drug reverses Alzheimer's disease deficits in mice." ScienceDaily. www.sciencedaily.com/releases/2013/05/130523143541.htm (accessed November 22, 2014).

Share This


More From ScienceDaily



More Mind & Brain News

Saturday, November 22, 2014

Featured Research

from universities, journals, and other organizations


Featured Videos

from AP, Reuters, AFP, and other news services

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
Your Complicated Job Might Keep Your Brain Young

Your Complicated Job Might Keep Your Brain Young

Newsy (Nov. 20, 2014) Researchers at the University of Edinburgh found the more complex your job is, the sharper your cognitive skills will likely be as you age. Video provided by Newsy
Powered by NewsLook.com
100-Year-Old Woman Sees Ocean for First Time

100-Year-Old Woman Sees Ocean for First Time

AP (Nov. 20, 2014) Ruby Holt spent most of her 100 years on a farm in rural Tennessee, picking cotton and raising four children. She saw the ocean for the first time thanks to her assisted living center and a group that grants wishes to the elderly. (Nov. 20) Video provided by AP
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