Featured Research

from universities, journals, and other organizations

Gene protects against dementia in high-risk individuals, study finds

Date:
December 30, 2010
Source:
Mayo Clinic
Summary:
Neuroscientists had assumed that a mutation in the progranulin gene, which makes the progranulin protein and supports brain neurons, was sufficient to produce a kind of dementia known as frontotemporal lobar degeneration. But now an international team of scientists has found another genetic factor they say appears to protect against the disorder in progranulin mutation carriers.

Neuroscientists had assumed that a mutation in the progranulin gene, which makes the progranulin protein and supports brain neurons, was sufficient to produce a kind of dementia known as frontotemporal lobar degeneration (FTLD). But now an international team of scientists led by researchers at Mayo Clinic's campus in Florida have found another genetic factor they say appears to protect against the disorder in progranulin mutation carriers.

Related Articles


In an article published in the Dec. 22, 2010, issue of Neurology, the medical journal of the American Academy of Neurology, the researchers report that people with a mutated progranulin gene who also inherited two copies of a specific variant of the TMEM106B gene are significantly less likely to develop FTLD or they have their disease onset delayed.

"This was an unexpected but very exciting finding because it suggests that if we could understand what TMEM106B is, and how it and its variants work, this could provide a new avenue for development of an agent that protects against FTLD," says the study's lead author, neuroscientist Rosa Rademakers, Ph.D.

The study was a follow-up to a genome-wide association study led by researchers from the University of Pennsylvania School of Medicine, which included 45 centers around the world and was published in March 2010 in Nature Genetics. This study used postmortem brain tissue to pinpoint variation in the TMEM106B gene as a risk factor for FTLD. What these patients all had in common was that they had lesions of misfolded TDP-43 proteins inside brain neurons. Researchers found that TMEM106B variants also played a role in FTLD patients with a progranulin mutation who invariably have these brain lesions.

"This research was designed to confirm the findings of the earlier study and to expand it to see if TMEM106B could modulate progranulin levels," Dr. Rademakers says. To do this, the researchers looked for the TMEM106B variant in a new set of patients, including 82 FTLD patients who had progranulin mutations, 562 FTLD patients without mutations, as well as a group of 822 healthy controls.

In the group as a whole, they did not see a significant association with TMEM106B, but there was a very significant association between TMEM106B variants and the development of FTLD in individuals with progranulin mutations.

The researchers found that individuals with a progranulin mutation who also inherited two copies of the protective TMEM106B allele did not develop FTLD or developed it at a much later age than is typical, which is normally around age 60, Dr. Rademakers says. "Since progranulin mutation carriers produce 50 percent less progranulin protein, we believe TMEM106B may affect progranulin levels and therefore specifically works in people with progranulin mutations," she says.

In support of their hypothesis, they found that individuals carrying the protective TMEM106B allele have more progranulin in their blood plasma, suggesting that the TMEM106B allele works to increase progranulin protein levels.

"The protective form of TMEM106B leads to higher levels of progranulin in the blood. Whether it also increases the levels of progranulin in the brain has not yet been studied and will be the focus of our future research," Dr. Rademakers says.

Not only could the beneficial TMEM106B allele be the basis of a novel therapy for individuals with a progranulin mutation, it might also help others who are at risk, for dementia she adds. "Subtle changes in progranulin levels have been linked to an increased risk for the development of FTLD, so now we have an interesting new lead to explore."

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


Story Source:

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


Journal Reference:

  1. N. Finch, M.M. Carrasquillo, M. Baker, N.J. Rutherford, G. Coppola, M. Dejesus-Hernandez, R. Crook, T. Hunter, R. Ghidoni, L. Benussi, J. Crook, E. Finger, K.J. Hantanpaa, A.M. Karydas, P. Sengdy, J. Gonzalez, W.W. Seeley, N. Johnson, T.G. Beach, M. Mesulam, G. Forloni, A. Kertesz, D.S. Knopman, R. Uitti, C.L. White III, R. Caselli, C. Lippa, E.H. Bigio, Z.K. Wszolek, G. Binetti, I.R. Mackenzie, B.L. Miller, B.F. Boeve, S.G. Younkin, D.W. Dickson, R.C. Petersen, N.R. Graff-Radford, D.H. Geschwind, R. Rademakers. TMEM106B regulates progranulin levels and the penetrance of FTLD in GRN mutation carriers. Neurology, 2010; DOI: 10.1212/WNL.0b013e31820a0e3b

Cite This Page:

Mayo Clinic. "Gene protects against dementia in high-risk individuals, study finds." ScienceDaily. ScienceDaily, 30 December 2010. <www.sciencedaily.com/releases/2010/12/101222162400.htm>.
Mayo Clinic. (2010, December 30). Gene protects against dementia in high-risk individuals, study finds. ScienceDaily. Retrieved December 20, 2014 from www.sciencedaily.com/releases/2010/12/101222162400.htm
Mayo Clinic. "Gene protects against dementia in high-risk individuals, study finds." ScienceDaily. www.sciencedaily.com/releases/2010/12/101222162400.htm (accessed December 20, 2014).

Share This


More From ScienceDaily



More Health & Medicine News

Saturday, December 20, 2014

Featured Research

from universities, journals, and other organizations


Featured Videos

from AP, Reuters, AFP, and other news services

The Best Tips to Curb Holiday Carbs

The Best Tips to Curb Holiday Carbs

Buzz60 (Dec. 19, 2014) It's hard to resist those delicious but fattening carbs we all crave during the winter months, but there are some ways to stay satisfied without consuming the extra calories. Vanessa Freeman (@VanessaFreeTV) has the details. Video provided by Buzz60
Powered by NewsLook.com
Sierra Leone Bikers Spread the Message to Fight Ebola

Sierra Leone Bikers Spread the Message to Fight Ebola

AFP (Dec. 19, 2014) More than 100 motorcyclists hit the road to spread awareness messages about Ebola. Nearly 7,000 people have now died from the virus, almost all of them in west Africa, according to the World Health Organization. Video provided by AFP
Powered by NewsLook.com
Researchers Test Colombian Village With High Alzheimer's Rates

Researchers Test Colombian Village With High Alzheimer's Rates

AFP (Dec. 19, 2014) In Yarumal, a village in N. Colombia, Alzheimer's has ravaged a disproportionately large number of families. A genetic "curse" that may pave the way for research on how to treat the disease that claims a new victim every four seconds. Duration: 02:42 Video provided by AFP
Powered by NewsLook.com
Double-Amputee Becomes First To Move Two Prosthetic Arms With His Mind

Double-Amputee Becomes First To Move Two Prosthetic Arms With His Mind

Buzz60 (Dec. 19, 2014) A double-amputee makes history by becoming the first person to wear and operate two prosthetic arms using only his mind. Jen Markham has the story. Video provided by Buzz60
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