Featured Research

from universities, journals, and other organizations

New Mechanism For Amyloid Beta Protein's Toxic Impact On The Alzheimer's Brain

Date:
July 6, 2009
Source:
Cell Press
Summary:
Scientists have uncovered a novel mechanism linking soluble amyloid b protein with the synaptic injury and memory loss associated with Alzheimer's disease (AD). The research provides critical new insight into disease pathogenesis and reveals signaling molecules that may serve as potential additional therapeutic targets for AD.

Scientists have uncovered a novel mechanism linking soluble amyloid ? protein with the synaptic injury and memory loss associated with Alzheimer's disease (AD). The research, published in the June 25 issue of the journal Neuron, provides critical new insight into disease pathogenesis and reveals signaling molecules that may serve as potential additional therapeutic targets for AD.

Amyloid ? protein (A?) plays a major pathogenic role in AD, a devastating neurodegenerative disorder characterized by progressive cognitive impairment and memory loss. "Given the mounting evidence that small soluble A? assemblies mediate synaptic impairment in AD, elucidating the precise molecular pathways by which this occurs has important implications for treating and preventing the disease," explains senior study author, Dr. Dennis Selkoe from the Center for Neurologic Diseases at Brigham and Women's Hospital and Harvard Medical School.

Dr. Selkoe, Dr. Shaomin Li, and colleagues examined regulation of a cellular communication phenomenon known as long-term synaptic depression (LTD). LTD has been linked with neuronal degeneration, but a role for A? in the regulation of LTD has not been clearly described. The researchers found that soluble A? facilitated LTD in the hippocampus, a region of the brain intimately associated with memory. The enhanced synaptic depression induced by soluble A? was mediated through a decrease in glutamate recycling at hippocampal synapses.

Excess glutamate, the major excitatory neurotransmitter in the brain, is thought to contribute to the progressive neuronal loss characteristic of AD. The researchers went on to show that A?-enhanced LTD was mediated by glutamate receptor activity and that the LTD could be prevented by an extracellular glutamate scavenger system. A very similar enhancement of LTD could be induced by a pharmacological blocker of glutamate reuptake. Importantly, soluble A? directly and significantly decreased glutamate uptake by isolated synapses.

"Our findings provide evidence that soluble A? from several sources enhances synaptic depression through a novel mechanism involving altered glutamate uptake at hippocampal synapses," concludes Dr. Selkoe. "These results have both mechanistic and therapeutic implications for the initiation of hippocampal synaptic failure in AD and in more subtle forms of age-related A? accumulation." Future studies are needed to determine precisely how soluble A? protein physically interferes with glutamate transporters at the synapse.

The researchers include Shaomin Li, Brigham and Women's Hospital, Harvard Medical School, Boston, MA; Soyon Hong, Brigham and Women's Hospital, Harvard Medical School, Boston, MA; Nina E. Shepardson, Brigham and Women's Hospital, Harvard Medical School, Boston, MA; Dominic M. Walsh, University College Dublin, Dublin, Ireland; Ganesh M. Shankar, Brigham and Women's Hospital, Harvard Medical School, Boston, MA; and Dennis Selkoe, Brigham and Women's Hospital, Harvard Medical School, Boston, MA.


Story Source:

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


Cite This Page:

Cell Press. "New Mechanism For Amyloid Beta Protein's Toxic Impact On The Alzheimer's Brain." ScienceDaily. ScienceDaily, 6 July 2009. <www.sciencedaily.com/releases/2009/06/090624153100.htm>.
Cell Press. (2009, July 6). New Mechanism For Amyloid Beta Protein's Toxic Impact On The Alzheimer's Brain. ScienceDaily. Retrieved August 28, 2014 from www.sciencedaily.com/releases/2009/06/090624153100.htm
Cell Press. "New Mechanism For Amyloid Beta Protein's Toxic Impact On The Alzheimer's Brain." ScienceDaily. www.sciencedaily.com/releases/2009/06/090624153100.htm (accessed August 28, 2014).

Share This




More Mind & Brain News

Thursday, August 28, 2014

Featured Research

from universities, journals, and other organizations


Featured Videos

from AP, Reuters, AFP, and other news services

Treadmill 'trips' May Reduce Falls for Elderly

Treadmill 'trips' May Reduce Falls for Elderly

AP (Aug. 28, 2014) Scientists are tripping the elderly on purpose in a Chicago lab in an effort to better prevent seniors from falling and injuring themselves in real life. (Aug.28) Video provided by AP
Powered by NewsLook.com
Alice in Wonderland Syndrome

Alice in Wonderland Syndrome

Ivanhoe (Aug. 27, 2014) It’s an unusual condition with a colorful name. Kids with “Alice in Wonderland” syndrome see sudden distortions in objects they’re looking at or their own bodies appear to change size, a lot like the main character in the Lewis Carroll story. Video provided by Ivanhoe
Powered by NewsLook.com
Stopping Schizophrenia Before Birth

Stopping Schizophrenia Before Birth

Ivanhoe (Aug. 27, 2014) Scientists have long called choline a “brain booster” essential for human development. Not only does it aid in memory and learning, researchers now believe choline could help prevent mental illness. Video provided by Ivanhoe
Powered by NewsLook.com
Personalized Brain Vaccine for Glioblastoma

Personalized Brain Vaccine for Glioblastoma

Ivanhoe (Aug. 27, 2014) Glioblastoma is the most common and aggressive brain cancer in humans. Now a new treatment using the patient’s own tumor could help slow down its progression and help patients live longer. Video provided by Ivanhoe
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