Featured Research

from universities, journals, and other organizations

MGH Study Identifies Potential Alzheimer's Risk Gene

Date:
March 11, 2005
Source:
Massachusetts General Hospital
Summary:
Researchers from the MassGeneral Institute for Neurodegenerative Disorders (MIND) have identified a gene variant that may increase the risk of late-onset Alzheimer's disease. In the March 3 New England Journal of Medicine they report that specific changes in the gene for a protein called ubiquilin-1 are associated with an increased incidence of Alzheimer's in two large study samples.

BOSTON - March 2, 2005 - Researchers from the MassGeneral Institute for Neurodegenerative Disorders (MIND) have identified a gene variant that may increase the risk of late-onset Alzheimer's disease. In the March 3 New England Journal of Medicine they report that specific changes in the gene for a protein called ubiquilin-1 are associated with an increased incidence of Alzheimer's in two large study samples. The discovery could lead to improved understanding of the disease mechanism and a new target for the development of preventive and treatment strategies.

"We believe this variant moderately but significantly raises the risk of Alzheimer's disease," says Lars Bertram, MD, of the Genetics and Aging Unit at MIND, lead author of the study. "We now have to pinpoint the biological defects that accompany this finding, which also needs to be independently replicated in other Alzheimer's sample groups." Bertram is an assistant professor of Neurology at Harvard Medical School (HMS).

Mutations that raise the risk of Alzheimer's have been found in four genes. Three of these - involving the amyloid precursor, presenilin 1 and presenilin 2 proteins - cause rare, inherited, early-onset forms of the devastating disorder. The only genetic variation associated with the more common late-onset form is ApoE4, which increases risk but does not directly cause the disease. Researchers expect that several additional genes that affect the risk of developing Alzheimer's may be found.

In 2003, the same research team published results of a full-genome screen of Alzheimer's patients and their affected siblings in a sample of 437 families compiled by the National Institute of Mental Health (NIMH). That study identified several potential chromosome "hotspots" that could be associated with increased risk, one of the strongest on chromosome 9. Since the gene for ubiquilin-1, which is known to interact with the presenilins, resides in the same area of chromosome 9, the researchers chose to test it as a candidate gene.

For the current study the investigators analyzed several sequence variations in ubiquilin-1 and two other candidate genes located nearby on chromosome 9. With the assistance of colleagues from Neurogenetics, Inc., the MIND researchers used a technique called family-based genetic association analysis to evaluate 19 sequence changes in these three genes, searching for alterations more likely to appear in patients with Alzheimer's. After first screening families from the same NIMH study group examined in the 2003 full-genome screen, they retested potential associations in a separate group of 217 sibling pairs. The results confirmed that particular changes in the ubiquilin-1 gene sequence occurred more frequently in individuals with Alzheimer's than in their unaffected siblings.

"The same variants of this gene conferred increased risk for Alzheimer's in both of these large study groups," says Rudolph Tanzi, PhD, director of the Genetics and Aging Unit and senior author of the study. "It was very encouraging to have the results confirmed in so many families."

The researchers then studied brain tissue from Alzheimer's patients and controls to see if the identified gene variants actually change the production of ubiquilin-1. In both groups, the same gene variants that increased the risk of Alzheimer's also led to increased production of a shorter form of ubiquilin-1, an overproduction that was even more pronounced in the patients. "Now we need to figure out what's wrong with too much ubiquilin-1 and with this different form," says Tanzi. "We need to look at how this variant interacts with the presenilins and what effect that may have on the production of A-beta," the protein that accumulates in the amyloid plaques found in the brains of Alzheimer's patients. Tanzi is a professor of Neurology at HMS.

The MGH researchers estimate that the increased risk accompanying these ubiquilin-1 gene variants is less than half that conferred by ApoE4. They and other research groups expect that 4 to 7 additional gene variants may be found that confer similar levels of risk.

Co-authors of the NEJM report are Mikko Hiltunen, PhD, Michelle Parkinson, Martin Ingelsson, MD, Karunya Ramasamy, Kristina Mullin, Rashmi Menon, Andrew Sampson, Monica Hsiao, Thomas Moscarillo, Bradley Hyman, MD, and Deborah Blacker, MD, ScD, all of the MGH; Christoph Lange, PhD, Harvard School of Public Health; and Kathryn Elliott, Gonul Velicelebi, PhD, Steven Wagner, PhD, and David Becker, PhD, Neurogenetics, Inc. The study was supported by grants from NIMH, the National Institute on Aging, the Alzheimer Association, the Deutsche Forschungsgemeinschaft, the Harvard Center for Neurodegeneration and Repair, and the National Alliance for Research on Schizophrenia and Depression.

Massachusetts General Hospital, established in 1811, is the original and largest teaching hospital of Harvard Medical School. The MGH conducts the largest hospital-based research program in the United States, with an annual research budget of more than $450 million and major research centers in AIDS, cardiovascular research, cancer, cutaneous biology, medical imaging, neurodegenerative disorders, transplantation biology and photomedicine. In 1994, MGH and Brigham and Women's Hospital joined to form Partners HealthCare System, an integrated health care delivery system comprising the two academic medical centers, specialty and community hospitals, a network of physician groups, and nonacute and home health services.


Story Source:

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


Cite This Page:

Massachusetts General Hospital. "MGH Study Identifies Potential Alzheimer's Risk Gene." ScienceDaily. ScienceDaily, 11 March 2005. <www.sciencedaily.com/releases/2005/03/050308101611.htm>.
Massachusetts General Hospital. (2005, March 11). MGH Study Identifies Potential Alzheimer's Risk Gene. ScienceDaily. Retrieved August 27, 2014 from www.sciencedaily.com/releases/2005/03/050308101611.htm
Massachusetts General Hospital. "MGH Study Identifies Potential Alzheimer's Risk Gene." ScienceDaily. www.sciencedaily.com/releases/2005/03/050308101611.htm (accessed August 27, 2014).

Share This




More Mind & Brain News

Wednesday, August 27, 2014

Featured Research

from universities, journals, and other organizations


Featured Videos

from AP, Reuters, AFP, and other news services

Have You Ever Been 'Sleep Drunk?' 1 in 7 Has

Have You Ever Been 'Sleep Drunk?' 1 in 7 Has

Newsy (Aug. 26, 2014) A study published in the journal "Neurology" interviewed more than 19,000 people and found 15 percent suffer from being "sleep drunk." Video provided by Newsy
Powered by NewsLook.com
Does Medical Marijuana Reduce Painkiller Overdose Deaths?

Does Medical Marijuana Reduce Painkiller Overdose Deaths?

Newsy (Aug. 26, 2014) A new study found fewer deaths from prescription drug overdoses in states that have legalized medical marijuana. But experts disagree on the results. Video provided by Newsy
Powered by NewsLook.com
Heart Group: E-Cigarettes May Help Smokers Quit

Heart Group: E-Cigarettes May Help Smokers Quit

AP (Aug. 25, 2014) The American Heart Association's first policy statement on electronic cigarettes backs them as a last resort to help smokers quit and calls for more regulation to keep them away from youth. (Aug. 25) Video provided by AP
Powered by NewsLook.com
Doctors Push For Later Start Times As School Year Kicks Off

Doctors Push For Later Start Times As School Year Kicks Off

Newsy (Aug. 25, 2014) The American Academy of Pediatrics is the latest group pushing for middle schools and high schools to start later, for the sake of their kids. Video provided by Newsy
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:
from the past week

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