Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

Two proteins may help prevent Alzheimer’s brain plaques

22.01.2004


A study led by researchers at Washington University School of Medicine in St. Louis suggests two proteins work together in mice to prevent formation of brain plaques characteristic of Alzheimer’s disease.



The proteins, apolipoprotein E (apoE) and clusterin, appear to act as "chaperones" orchestrating the clearance of potentially hazardous molecules out of the brain. Ironically, these proteins also have been implicated in a key stage of plaque formation. The study appears in the Jan. 22 issue of the journal Neuron.

"This is one of the first demonstrations in living animals that these proteins affect amyloid clearance," says David H. Holtzman, M.D., the Andrew B. and Gretchen P. Jones Professor and head of the Department of Neurology. "Our findings suggest it is worthwhile to explore the use of drugs or therapies to alter or perhaps increase the expression of these proteins as a potential treatment for Alzheimer’s disease."


Holtzman, who also is the Charlotte and Paul Hagemann Professor of Neurology and professor of molecular biology and pharmacology, led the study; Ronald DeMattos, Ph.D., formerly an instructor in neurology, and John R. Cirrito, a graduate student in neuroscience, are co-first authors. The team collaborated with Eli Lilly and Company, where DeMattos now works.

A key step in the development of Alzheimer’s disease is the formation of brain plaques. Studies suggest these plaques form when the protein amyloid beta (Abeta) is converted from its soluble to its insoluble form and coalesces into hair-shaped threads called fibrils. Unable to dissolve or be cleared out of the brain, the fibrils eventually clump together and become the amyloid plaques that are a hallmark of Alzheimer’s.

In previous studies, Holtzman’s team was instrumental in showing both apoE and clusterin promote the formation of these fibrils. Their new paper confirms that in mice genetically engineered to develop Alzheimer’s disease-like brain plaques, those without either apoE or clusterin developed fewer fibrils.

The team therefore expected mice lacking both proteins would develop even fewer deposits. However, the opposite was true. Moreover, fibrils in animals lacking both proteins developed significantly earlier in life and resulted in the more advanced amyloid plaques. Such extreme Abeta deposition at a young age is akin to that in humans with the rare, genetic form of the disease called familial Alzheimer’s.

"This was an unexpected and striking result," Holtzman says. "Though at first counter-intuitive, it implies that apoE and clusterin cooperate to suppress Abeta deposition."

In addition to increased amounts of Abeta in brain tissue, the team also found abnormally high levels in the fluid surrounding individual brain cells and in the fluid surrounding the entire brain. In contrast, levels of Abeta in the blood were not abnormally high.

Combined, the results suggest the two proteins not only play a role in the development of fibrils, but also in the clearance of Abeta from brain tissue and surrounding fluid. Without its chaperones, Abeta protein settles in the brain and eventually clusters into plaques.

According to Holtzman, the next step is to determine whether human forms of apoE and clusterin also delay or prevent the development of plaques in the mouse model and to explore the potential for drugs or gene therapy to reverse plaque formation in mice.


DeMattos RB, Cirrito JR, Parsadanian M, May PC, O’Dell MA, Tayler JW, Harmony JAK, Aronow BJ, Bales KR, Paul SM, Holtzman DM. ApoE and clusterin cooperatively suppress Abeta levels and deposition: Evidence at apoE regulates extracellular Abeta metabolism in vivo. Neuron, Jan. 22, 2004.

Funding from the National Institutes of Health, MetLife Foundation and Eli Lilly and Company supported this research.

The full-time and volunteer faculty of Washington University School of Medicine are the physicians and surgeons of Barnes-Jewish and St. Louis Children’s hospitals. The School of Medicine is one of the leading medical research, teaching and patient-care institutions in the nation. Through its affiliations with Barnes-Jewish and St. Louis Children’s hospitals, the School of Medicine is linked to BJC HealthCare.

Gila Z. Reckess | WUSTL
Further information:
http://aladdin.wustl.edu/medadmin/PAnews.nsf/news/4FEF72B0382045EE86256E21007A8CFB?OpenDocument
http://medinfo.wustl.edu/

More articles from Health and Medicine:

nachricht 3D images of cancer cells in the body: Medical physicists from Halle present new method
16.05.2018 | Martin-Luther-Universität Halle-Wittenberg

nachricht Better equipped in the fight against lung cancer
16.05.2018 | Friedrich-Alexander-Universität Erlangen-Nürnberg

All articles from Health and Medicine >>>

The most recent press releases about innovation >>>

Die letzten 5 Focus-News des innovations-reports im Überblick:

Im Focus: LZH showcases laser material processing of tomorrow at the LASYS 2018

At the LASYS 2018, from June 5th to 7th, the Laser Zentrum Hannover e.V. (LZH) will be showcasing processes for the laser material processing of tomorrow in hall 4 at stand 4E75. With blown bomb shells the LZH will present first results of a research project on civil security.

At this year's LASYS, the LZH will exhibit light-based processes such as cutting, welding, ablation and structuring as well as additive manufacturing for...

Im Focus: Self-illuminating pixels for a new display generation

There are videos on the internet that can make one marvel at technology. For example, a smartphone is casually bent around the arm or a thin-film display is rolled in all directions and with almost every diameter. From the user's point of view, this looks fantastic. From a professional point of view, however, the question arises: Is that already possible?

At Display Week 2018, scientists from the Fraunhofer Institute for Applied Polymer Research IAP will be demonstrating today’s technological possibilities and...

Im Focus: Explanation for puzzling quantum oscillations has been found

So-called quantum many-body scars allow quantum systems to stay out of equilibrium much longer, explaining experiment | Study published in Nature Physics

Recently, researchers from Harvard and MIT succeeded in trapping a record 53 atoms and individually controlling their quantum state, realizing what is called a...

Im Focus: Dozens of binaries from Milky Way's globular clusters could be detectable by LISA

Next-generation gravitational wave detector in space will complement LIGO on Earth

The historic first detection of gravitational waves from colliding black holes far outside our galaxy opened a new window to understanding the universe. A...

Im Focus: Entangled atoms shine in unison

A team led by Austrian experimental physicist Rainer Blatt has succeeded in characterizing the quantum entanglement of two spatially separated atoms by observing their light emission. This fundamental demonstration could lead to the development of highly sensitive optical gradiometers for the precise measurement of the gravitational field or the earth's magnetic field.

The age of quantum technology has long been heralded. Decades of research into the quantum world have led to the development of methods that make it possible...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

VideoLinks
Industry & Economy
Event News

Save the date: Forum European Neuroscience – 07-11 July 2018 in Berlin, Germany

02.05.2018 | Event News

Invitation to the upcoming "Current Topics in Bioinformatics: Big Data in Genomics and Medicine"

13.04.2018 | Event News

Unique scope of UV LED technologies and applications presented in Berlin: ICULTA-2018

12.04.2018 | Event News

 
Latest News

Designer cells: artificial enzyme can activate a gene switch

22.05.2018 | Life Sciences

PR of MCC: Carbon removal from atmosphere unavoidable for 1.5 degree target

22.05.2018 | Earth Sciences

Achema 2018: New camera system monitors distillation and helps save energy

22.05.2018 | Trade Fair News

VideoLinks
Science & Research
Overview of more VideoLinks >>>