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 Organ-on-a-chip mimics heart's biomechanical properties
23.02.2017 | Vanderbilt University

nachricht Researchers identify cause of hereditary skeletal muscle disorder
22.02.2017 | Klinikum der Universität München

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: Breakthrough with a chain of gold atoms

In the field of nanoscience, an international team of physicists with participants from Konstanz has achieved a breakthrough in understanding heat transport

In the field of nanoscience, an international team of physicists with participants from Konstanz has achieved a breakthrough in understanding heat transport

Im Focus: DNA repair: a new letter in the cell alphabet

Results reveal how discoveries may be hidden in scientific “blind spots”

Cells need to repair damaged DNA in our genes to prevent the development of cancer and other diseases. Our cells therefore activate and send “repair-proteins”...

Im Focus: Dresdner scientists print tomorrow’s world

The Fraunhofer IWS Dresden and Technische Universität Dresden inaugurated their jointly operated Center for Additive Manufacturing Dresden (AMCD) with a festive ceremony on February 7, 2017. Scientists from various disciplines perform research on materials, additive manufacturing processes and innovative technologies, which build up components in a layer by layer process. This technology opens up new horizons for component design and combinations of functions. For example during fabrication, electrical conductors and sensors are already able to be additively manufactured into components. They provide information about stress conditions of a product during operation.

The 3D-printing technology, or additive manufacturing as it is often called, has long made the step out of scientific research laboratories into industrial...

Im Focus: Mimicking nature's cellular architectures via 3-D printing

Research offers new level of control over the structure of 3-D printed materials

Nature does amazing things with limited design materials. Grass, for example, can support its own weight, resist strong wind loads, and recover after being...

Im Focus: Three Magnetic States for Each Hole

Nanometer-scale magnetic perforated grids could create new possibilities for computing. Together with international colleagues, scientists from the Helmholtz Zentrum Dresden-Rossendorf (HZDR) have shown how a cobalt grid can be reliably programmed at room temperature. In addition they discovered that for every hole ("antidot") three magnetic states can be configured. The results have been published in the journal "Scientific Reports".

Physicist Dr. Rantej Bali from the HZDR, together with scientists from Singapore and Australia, designed a special grid structure in a thin layer of cobalt in...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

Booth and panel discussion – The Lindau Nobel Laureate Meetings at the AAAS 2017 Annual Meeting

13.02.2017 | Event News

Complex Loading versus Hidden Reserves

10.02.2017 | Event News

International Conference on Crystal Growth in Freiburg

09.02.2017 | Event News

 
Latest News

Stingless bees have their nests protected by soldiers

24.02.2017 | Life Sciences

New risk factors for anxiety disorders

24.02.2017 | Life Sciences

MWC 2017: 5G Capital Berlin

24.02.2017 | Trade Fair News

VideoLinks
B2B-VideoLinks
More VideoLinks >>>