Featured Research

from universities, journals, and other organizations

Biochemical pathway by which harmful molecule may raise Alzheimer's risk uncovered

Date:
June 17, 2010
Source:
UT Southwestern Medical Center
Summary:
A molecule implicated in Alzheimer's disease interferes with brain cells by making them unable to "recycle" the surface receptors that respond to incoming signals, researchers have found.

A molecule implicated in Alzheimer's disease interferes with brain cells by making them unable to "recycle" the surface receptors that respond to incoming signals, researchers at UT Southwestern Medical Center have found.

The harmful molecule, called APOE4, is present in about one out of every six people, the researchers said. Those with the gene for APOE4 have up to 10 times the risk of developing Alzheimer's disease earlier in life than average.

The researchers discovered that APOE4 makes a nerve cell hold back the molecules that enables it to respond to other cells, thereby disabling a chemical process known to be important in learning. Their findings appear online in the Proceedings of the National Academy of Sciences.

"This is actually a fairly simple system," said Dr. Joachim Herz, director of the Center for Alzheimer's and Neurodegenerative Disease at UT Southwestern and senior author of the study. "For the first time, we see an uninterrupted biochemical pathway that links the surface of the brain cell to the dysfunction inside the cell, and specifically at the junction at which nerve cells communicate."

The research focused on a basic characteristic of nerve cells called neurotransmission, in which they use chemicals to signal each other. When one nerve cell needs to "talk" to another, its tip sends out a chemical called a neurotransmitter. The surface of the second cell is studded with molecules called receptors, which fit specific neurotransmitters like a lock and key. When a neurotransmitter docks onto its receptor, the second cell responds.

A cell can fine-tune its sensitivity by removing receptors from its surface. To do this, the cell engulfs the receptors to its interior, taking them out of action. It can eventually recycle them back to the surface, where they can respond to neurotransmitters again.

The researchers looked at receptors that respond to a neurotransmitter called glutamate, which is implicated in memory and learning. In mice that were genetically altered to make human APOE4, the researchers found that APOE4 prevented the cells from accomplishing a vital step in learning -- becoming more sensitive to repeated signals.

The researchers also studied the mice's hippocampus -- an area of the brain vital to learning -- to see how it would respond to extracts from the brain of a human with Alzheimer's. The extract prevented both normal and genetically altered mice from processing incoming signals; however, the normal mice could recover from this suppression, while the mice with APOE4 could not.

Dr. Herz and his colleagues hypothesized that APOE4 exerted its effects by interacting with the receptors for a molecule called Reelin, which keeps brain cells more sensitive to each other. Both APOE4 and Reelin bind to the same receptor. When Reelin binds to it, the combination triggers a biochemical cascade that makes the glutamate receptor more sensitive to incoming signals.

The researchers showed that APOE4 prevents the Reelin-binding receptor from being recycled back to the surface. With fewer receptors, the nerve cell can't bind much Reelin, no matter how much is around. Without Reelin's effects, the cell doesn't respond as vigorously to glutamate, and doesn't "learn" as well.

Knowing how a biological system works doesn't automatically translate to clinical use, Dr. Herz cautioned. "Although these findings constitute a milestone in our understanding of how APOE4 becomes such a potent risk factor for Alzheimer's disease, potential drugs that might come from this finding would still require years of development," he said.

"The question is, now that we've apparently identified what's going on, can we do anything about this disease process at the fundamental molecular level? That's what we're working on right now," Dr. Herz said.

Other UT Southwestern researchers involved in the study were graduate student Ying Chen; Dr. Murat Durakoglugil, assistant instructor of molecular genetics; and Dr. Xunde Xian, postdoctoral researcher in molecular genetics.

The study was funded by the National Institutes of Health, the American Health Assistance Foundation, the Perot Family Foundation, the Consortium for Frontotemporal Dementia Research, SFB780 and the Humboldt Foundation.


Story Source:

The above story is based on materials provided by UT Southwestern Medical Center. Note: Materials may be edited for content and length.


Journal Reference:

  1. Ying Chen, Murat S. Durakoglugil, Xunde Xian, and Joachim Herz. ApoE4 reduces glutamate receptor function and synaptic plasticity by selectively impairing ApoE receptor recycling. Proceedings of the National Academy of Sciences, 2010; DOI: 10.1073/pnas.0914984107

Cite This Page:

UT Southwestern Medical Center. "Biochemical pathway by which harmful molecule may raise Alzheimer's risk uncovered." ScienceDaily. ScienceDaily, 17 June 2010. <www.sciencedaily.com/releases/2010/06/100614160207.htm>.
UT Southwestern Medical Center. (2010, June 17). Biochemical pathway by which harmful molecule may raise Alzheimer's risk uncovered. ScienceDaily. Retrieved April 17, 2014 from www.sciencedaily.com/releases/2010/06/100614160207.htm
UT Southwestern Medical Center. "Biochemical pathway by which harmful molecule may raise Alzheimer's risk uncovered." ScienceDaily. www.sciencedaily.com/releases/2010/06/100614160207.htm (accessed April 17, 2014).

Share This



More Health & Medicine News

Thursday, April 17, 2014

Featured Research

from universities, journals, and other organizations


Featured Videos

from AP, Reuters, AFP, and other news services

Could Even Casual Marijuana Use Alter Your Brain?

Could Even Casual Marijuana Use Alter Your Brain?

Newsy (Apr. 16, 2014) A new study conducted by researchers at Northwestern and Harvard suggests even casual marijuana use can alter your brain. Video provided by Newsy
Powered by NewsLook.com
Thousands Of Vials Of SARS Virus Go Missing

Thousands Of Vials Of SARS Virus Go Missing

Newsy (Apr. 16, 2014) A research institute in Paris somehow misplaced more than 2,000 vials of the deadly SARS virus. Video provided by Newsy
Powered by NewsLook.com
Formerly Conjoined Twins Released From Dallas Hospital

Formerly Conjoined Twins Released From Dallas Hospital

Newsy (Apr. 16, 2014) Conjoined twins Emmett and Owen Ezell were separated by doctors in August. Now, nearly nine months later, they're being released from the hospital. Video provided by Newsy
Powered by NewsLook.com
Ebola Outbreak Now Linked To 121 Deaths

Ebola Outbreak Now Linked To 121 Deaths

Newsy (Apr. 15, 2014) The ebola virus outbreak in West Africa is now linked to 121 deaths. Health officials fear the virus will continue to spread in urban areas. 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:
from the past week

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