Featured Research

from universities, journals, and other organizations

New understanding of Alzheimer's trigger

Date:
May 2, 2012
Source:
University of Virginia
Summary:
A highly toxic beta-amyloid – a protein that exists in the brains of Alzheimer's disease victims – has been found to greatly increase the toxicity of other more common and less toxic beta-amyloids, serving as a possible "trigger" for the advent and development of Alzheimer's, researchers have discovered.

Pyroglutanylated beta-amyloid (green) accumulates in the brains of mice genetically engineered to overproduce it. The red cells are astrocytes, which invade brain regions where the amyloid is deposited and neurons die. The blue structures are nuclei of neurons and astrocytes.
Credit: University of Virginia

A highly toxic beta-amyloid -- a protein that exists in the brains of Alzheimer's disease victims -- has been found to greatly increase the toxicity of other more common and less toxic beta-amyloids, serving as a possible "trigger" for the advent and development of Alzheimer's, researchers at the University of Virginia and German biotech company Probiodrug have discovered.

Related Articles


The finding, reported in the May 2 online edition of the journal Nature, could lead to more effective treatments for Alzheimer's. Already, Probiodrug AG, based in Halle, Germany has completed phase 1 clinical trials in Europe with a small molecule that inhibits an enzyme, glutaminyl cyclase, that catalyzes the formation of this hypertoxic version of beta-amyloid.

"This form of beta-amyloid, called pyroglutamylated (or pyroglu) beta-amyloid, is a real bad guy in Alzheimer's disease," said principal investigator George Bloom, a U.Va. professor of biology and cell biology in the College of Arts & Sciences and School of Medicine, who is collaborating on the study with scientists at Probiodrug. "We've confirmed that it converts more abundant beta-amyloids into a form that is up to 100 times more toxic, making this a very dangerous killer of brain cells and an attractive target for drug therapy."

Bloom said the process is similar to various prion diseases, such as mad cow disease or chronic wasting disease, where a toxic protein can "infect" normal proteins that spread through the brain and ultimately destroy it.

In the case of Alzheimer's, severe dementia occurs over the course of years prior to death.

"You might think of this pyroglu beta-amyloid as a seed that can further contaminate something that's already bad into something much worse -- it's the trigger," Bloom said. Just as importantly, the hypertoxic mixtures that are seeded by pyroglu beta-amyloid exist as small aggregates, called oligomers, rather than as much larger fibers found in the amyloid plaques that are a signature feature of the Alzheimer's brain.

And the trigger fires a "bullet," as Bloom puts it. The bullet is a protein called tau that is stimulated by beta-amyloid to form toxic "tangles" in the brain that play a major role in the onset and development of Alzheimer's. Using mice bred to have no tau genes, the researchers found that without the interaction of toxic beta-amyloids with tau, the Alzheimer's cascade cannot begin. The pathway by which pyroglu beta-amyloid induces the tau-dependent death of neurons is now the target of further investigation to understand this important step in the early development of Alzheimer's disease

"There are two matters of practical importance in our discovery," Bloom said. "One, is the new insights we have as to how Alzheimer's might actually progress -- the mechanisms which are important to understand if we are to try to prevent it from happening; and second, it provides a lead into how to design drugs that might prevent this kind of beta-amyloid from building up in the first place."

Said study co-author Hans-Ulrich Demuth, a biochemist and chief scientific officer at Probiodrug, "This publication further adds significant evidence to our hypothesis about the critical role pyroglu beta-amyloid plays in the initiation of Alzheimer's Disease. For the first time we have found a clear link in the relationship between pyroglu beta-amyloid, oligomer formation and tau protein in neuronal toxicity."

Bloom and his collaborators are now looking for other proteins that are needed for pyroglu beta-amyloid to become toxic. Any such proteins they discover are potential targets for the early diagnosis and/or treatment of Alzheimer's disease.


Story Source:

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


Journal Reference:

  1. Justin M. Nussbaum, Stephan Schilling, Holger Cynis, Antonia Silva, Eric Swanson, Tanaporn Wangsanut, Kaycie Tayler, Brian Wiltgen, Asa Hatami, Raik Rφnicke, Klaus Reymann, Birgit Hutter-Paier, Anca Alexandru, Wolfgang Jagla, Sigrid Graubner, Charles G. Glabe, Hans-Ulrich Demuth, George S. Bloom. Prion-like behaviour and tau-dependent cytotoxicity of pyroglutamylated amyloid-β. Nature, 2012; DOI: 10.1038/nature11060

Cite This Page:

University of Virginia. "New understanding of Alzheimer's trigger." ScienceDaily. ScienceDaily, 2 May 2012. <www.sciencedaily.com/releases/2012/05/120502132956.htm>.
University of Virginia. (2012, May 2). New understanding of Alzheimer's trigger. ScienceDaily. Retrieved April 20, 2015 from www.sciencedaily.com/releases/2012/05/120502132956.htm
University of Virginia. "New understanding of Alzheimer's trigger." ScienceDaily. www.sciencedaily.com/releases/2012/05/120502132956.htm (accessed April 20, 2015).

Share This


More From ScienceDaily



More Mind & Brain News

Monday, April 20, 2015

Featured Research

from universities, journals, and other organizations


Featured Videos

from AP, Reuters, AFP, and other news services

Our Love Of Puppy Dog Eyes Explained By Science

Our Love Of Puppy Dog Eyes Explained By Science

Newsy (Apr. 17, 2015) — Researchers found a spike in oxytocin occurs in both humans and dogs when they gaze into each other&apos;s eyes. Video provided by Newsy
Powered by NewsLook.com
Scientists Find Link Between Gestational Diabetes And Autism

Scientists Find Link Between Gestational Diabetes And Autism

Newsy (Apr. 17, 2015) — Researchers who analyzed data from over 300,000 kids and their mothers say they&apos;ve found a link between gestational diabetes and autism. Video provided by Newsy
Powered by NewsLook.com
Video Messages Help Reassure Dementia Patients

Video Messages Help Reassure Dementia Patients

AP (Apr. 17, 2015) — Family members are prerecording messages as part of a unique pilot program at the Hebrew Home in New York. The videos are trying to help victims of Alzheimer&apos;s disease and other forms of dementia break through the morning fog of forgetfulness. (April 17) Video provided by AP
Powered by NewsLook.com
Common Pain Reliever Might Dull Your Emotions

Common Pain Reliever Might Dull Your Emotions

Newsy (Apr. 16, 2015) — Each week, millions of Americans take acetaminophen to dull minor aches and pains. Now researchers say it might blunt life&apos;s highs and lows, too. 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