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 BigH1 -- The key histone for male fertility
14.12.2017 | Institute for Research in Biomedicine (IRB Barcelona)

nachricht Guardians of the Gate
14.12.2017 | Max-Planck-Institut für Biochemie

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

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

Im Focus: Long-lived storage of a photonic qubit for worldwide teleportation

MPQ scientists achieve long storage times for photonic quantum bits which break the lower bound for direct teleportation in a global quantum network.

Concerning the development of quantum memories for the realization of global quantum networks, scientists of the Quantum Dynamics Division led by Professor...

Im Focus: Electromagnetic water cloak eliminates drag and wake

Detailed calculations show water cloaks are feasible with today's technology

Researchers have developed a water cloaking concept based on electromagnetic forces that could eliminate an object's wake, greatly reducing its drag while...

Im Focus: Scientists channel graphene to understand filtration and ion transport into cells

Tiny pores at a cell's entryway act as miniature bouncers, letting in some electrically charged atoms--ions--but blocking others. Operating as exquisitely sensitive filters, these "ion channels" play a critical role in biological functions such as muscle contraction and the firing of brain cells.

To rapidly transport the right ions through the cell membrane, the tiny channels rely on a complex interplay between the ions and surrounding molecules,...

Im Focus: Towards data storage at the single molecule level

The miniaturization of the current technology of storage media is hindered by fundamental limits of quantum mechanics. A new approach consists in using so-called spin-crossover molecules as the smallest possible storage unit. Similar to normal hard drives, these special molecules can save information via their magnetic state. A research team from Kiel University has now managed to successfully place a new class of spin-crossover molecules onto a surface and to improve the molecule’s storage capacity. The storage density of conventional hard drives could therefore theoretically be increased by more than one hundred fold. The study has been published in the scientific journal Nano Letters.

Over the past few years, the building blocks of storage media have gotten ever smaller. But further miniaturization of the current technology is hindered by...

Im Focus: Successful Mechanical Testing of Nanowires

With innovative experiments, researchers at the Helmholtz-Zentrums Geesthacht and the Technical University Hamburg unravel why tiny metallic structures are extremely strong

Light-weight and simultaneously strong – porous metallic nanomaterials promise interesting applications as, for instance, for future aeroplanes with enhanced...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

See, understand and experience the work of the future

11.12.2017 | Event News

Innovative strategies to tackle parasitic worms

08.12.2017 | Event News

AKL’18: The opportunities and challenges of digitalization in the laser industry

07.12.2017 | Event News

 
Latest News

Plasmonic biosensors enable development of new easy-to-use health tests

14.12.2017 | Health and Medicine

New type of smart windows use liquid to switch from clear to reflective

14.12.2017 | Physics and Astronomy

BigH1 -- The key histone for male fertility

14.12.2017 | Life Sciences

VideoLinks
B2B-VideoLinks
More VideoLinks >>>