Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

New Insight into the Cause of Common Dementia Found by Researchers at Mayo Clinic

18.11.2010
Researchers at the Mayo Clinic campus in Florida have found a clue as to how some people develop a form of dementia that affects the brain areas associated with personality, behavior, and language.

In the Nov. 17 online issue of the American Journal of Human Genetics, the scientists write that they discovered a link between two proteins — progranulin and sortilin — they say might open new avenues for the treatment of frontotemporal lobar degeneration (FTLD), which occurs in the frontal lobe and temporal lobe of the brain.

This form of dementia, which is currently untreatable, generally occurs in younger people, compared to other common neurodegenerative disorders such as Alzheimer's disease.

"We now can look for a direct link between these two proteins and the development of FTLD," says the study's lead author, neuroscientist Rosa Rademakers, Ph.D. "The hope is that if we do find a strong association, it might be possible to manipulate levels of one or both of these proteins therapeutically."

Coincidentally, a research group from Yale University led by Stephen Strittmatter, M.D., Ph.D., has also pinpointed sortilin's association with progranulin — thus confirming Mayo's results. Their study is being published in Neuron, also on Nov. 17.

FTLD is a family of brain diseases that are believed to share some common molecular features. One is the presence of mutations in the gene that produces tau protein in neurons. The other is mutations in the progranulin gene that Mayo Clinic researchers and their colleagues discovered in 2006. They found that 5 to 10 percent of patients with FTLD have a mutation in this gene, and that these mutations lead to a substantial loss of normal progranulin protein production, and development of FTLD.

The protein made by the progranulin gene is found throughout the body, and performs different functions according to the type of tissue (organ) it is located in. But in the brain, it is believed to support neurons and keep them healthy.

Still, researchers do not really know how normal progranulin protein functions in the brain — what other proteins it interacts with — and so in this study they sought to uncover clues about progranulin biology by conducting a genome-wide association study (GWAS).

Based on their previous findings that a simple blood test is able to measure progranulin levels in plasma and could be used to identify patients with progranulin mutations, they tested blood from 518 healthy individuals in a GWAS to look for genetic variants that could explain some of the normal variability of progranulin levels in plasma. They found very strong association with two genetic variants in the same region of chromosome 1 and confirmed this finding in a second group of 495 healthy individuals.

By reviewing the scientific literature, they further ascertained that the same genetic variant found to be associated with plasma progranulin levels also affects the levels of the protein sortilin. Like progranulin, sortilin is found throughout the body and is involved in different tasks. In the brain, it is known to be important for survival of brain neurons.

"So, using a genetic approach, we identified a previously unknown connection between sortilin and progranulin," Dr. Rademakers says.

The researchers then studied the two proteins in cell culture and showed that the amount of sortilin in cells determines how much progranulin is taken inside or remains outside of a cell. "Our study shows that changes in the levels of sortilin result in different levels of progranulin available to cells. Given that we found FTLD patients often have less progranulin than they should, we believe that if you can manipulate levels of progranulin and/or sortilin in the brain, you might have a way to treat this disorder," says Dr. Rademakers.

"Our study and the study led by the Yale researchers describe completely independent and unbiased screens which both identified this protein sortilin as being important in the regulation of progranulin," Dr. Rademakers says. "This obviously opens new avenues for treatment for patients with progranulin mutations and perhaps dementia patients in general."

Researchers from the National Institutes of Health, University College London, the University of British Columbia, and Mayo Clinic in Minnesota also participated in this study.

The study was funded by the National Institutes of Health and the Consortium for Frontotemporal Dementia Research. The authors declare no conflicts of interest.

About Mayo Clinic
Mayo Clinic is the first and largest integrated, not-for-profit group practice in the world. Doctors from every medical specialty work together to care for patients, joined by common systems and a philosophy of "the needs of the patient come first." More than 3,700 physicians, scientists and researchers, and 50,100 allied health staff work at Mayo Clinic, which has campuses in Rochester, Minn; Jacksonville, Fla; and Scottsdale/Phoenix, Ariz.; and community-based providers in more than 70 locations in southern Minnesota., western Wisconsin and northeast Iowa. These locations treat more than half a million people each year. To obtain the latest news releases from Mayo Clinic, go to www.mayoclinic.org/news. For information about research and education, visit www.mayo.edu. MayoClinic.com (www.mayoclinic.com) is available as a resource for your health stories.

Kevin Punsky | EurekAlert!
Further information:
http://www.mayo.edu

More articles from Life Sciences:

nachricht New risk factors for anxiety disorders
24.02.2017 | Julius-Maximilians-Universität Würzburg

nachricht Stingless bees have their nests protected by soldiers
24.02.2017 | Johannes Gutenberg-Universität Mainz

All articles from Life Sciences >>>

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 >>>