Featured Research

from universities, journals, and other organizations

Eleven new genetic susceptibility factors for Alzheimer's disease discovered through the largest study

Date:
October 27, 2013
Source:
Boston University Medical Center
Summary:
The largest international study ever conducted on Alzheimer's disease (AD), the I-GAP (International Genomics Alzheimer's Project) consortium has identified 11 new regions of the genome involved in the onset of this neurodegenerative disease. This study gives an overview of the molecular mechanisms underlying the disease, opening up to a better understanding of the pathophysiology of AD.

Since 2009, 10 genes for Alzheimer's disease have been identified. However, much of the individual susceptibility to develop the disease remains unexplained. 11 newly confirmed genes may open new avenues to understanding the causes of AD.
Credit: Tomasz / Fotolia

The largest international study ever conducted on Alzheimer's disease (AD), the I-GAP (International Genomics Alzheimer's Project) consortium has identified 11 new regions of the genome involved in the onset of this neurodegenerative disease. This study gives an overview of the molecular mechanisms underlying the disease, opening up to a better understanding of the pathophysiology of AD. These results detailed currently in Nature Genetics, could not have been obtained without this unique worldwide collaborative effort.

Since 2009, 10 genes for Alzheimer's disease have been identified. However, much of the individual susceptibility to develop the disease remains unexplained. So in February 2011, the leaders of the four largest international research consortia on the genetics of AD joined forces to accelerate the discovery of new genes. Supported in part by the National Institute on Aging (NIA) and other components of the National Institutes of Health (NIH), in less than three years, the IGAP program identified more genes than had been identified over the previous 20 years. They collected genetic data on 74,076 patients and controls from 15 countries and were able to discover 11 new genes in addition to those already known, and identify 13 other genes, yet to be validated.

These 11 new confirmed genes may open new avenues to understanding the causes of AD. For example, one of the most significant associations was found in the region HLA-DRB5/DRB1 major histocompatibility complex. This finding is interesting in several ways. First, it strongly suggests the involvement of the immune system in AD. In addition, this same region has also been associated with two other neurodegenerative diseases, one known to have an immune mechanism, multiple sclerosis and another not previously thought to have a major immune component, Parkinson's disease.

Some of the newly associated genes confirm biological pathways known to be involved in AD, including the amyloid (SORL1, CASS4 ) and tau (CASS4 , FERMT2 ) pathways. The role of the immune response and inflammation (HLA-DRB5/DRB1 , INPP5D , MEF2C ) already implied by previous work (CR1, TREM2) is reinforced, as are the importance of cell migration (PTK2B), lipid transport and endocytosis (SORL1 ). New hypotheses have also emerged related to hippocampal synaptic function (MEF2C , PTK2B), the cytoskeleton and axonal transport (CELF1 , NME8, CASS4) as well as myeloid and microglial cell functions (INPP5D).

Finally, this work demonstrates that, given the complexity of such a disease, only a global collaboration of research efforts will quickly find solutions to tackle this major threat.

The four founding partners in this international consortium are, in alphabetical order, the Alzheimer's Disease Genetics Consortium (ADGC), the Cohorts for Heart and Aging Research in Genomic Epidemiology (CHARGE), the European Alzheimer Disease Initiative (EADI) and the Genetic and Environmental Research in Alzheimer Disease (GERAD) consortium.

Boston University and the Framingham Heart Study are well-represented in this landmark international effort. The neurology working group of the Cohorts for Heart and Aging Research in Genomic Epidemiology is led by Sudha Seshadri, MD, professor of neurology at Boston University School of Medicine (BUSM), who is a senior investigator in the Framingham Heart Study and also one of the senior authors on this manuscript. Several other senior investigators, notably Anita L. DeStefano , PhD, professor of biostatistics Boston University School of Public Health (BUSPH) on behalf of CHARGE, and Lindsay A. Farrer, PhD, Chief of Biomedical Genetics and professor of medicine, neurology, ophthalmology, genetics & genomics, epidemiology, and biostatistics at BUSM and BUSPH on behalf of the ADGC, were key investigators in this effort. Farrer co-directs the data analysis effort for the ADGC which includes nearly all of the nation's researchers working on the genetics of AD as well as many investigators and resources of the 29 NIA funded Alzheimer Disease Centers.

"This study clearly demonstrates that there really is strength in numbers to identify genes that individually have a small effect on risk of Alzheimer's," said Farrer. "But it's not the magnitude of the odds ratio that's really important. Each gene we implicate in the disease process adds new knowledge to our understanding of disease mechanism and provides insight into developing new therapeutic approaches, and ultimately these approaches may be more effective in halting the disease since genes are expressed long before clinical symptoms appear and brain damage occurs," he added.

"This landmark international effort has uncovered new pathways and new genes in old pathways that are definitely associated with Alzheimer dementia, but we need to do much work to better understand how exactly these genes work in health and disease, and to perhaps make drugs from these genes and molecules," said Seshadri. "We will continue to mine these results for new insights, even as we include more patients and use new technologies like whole genome sequencing to find more new pathways and genes," she added.


Story Source:

The above story is based on materials provided by Boston University Medical Center. Note: Materials may be edited for content and length.


Journal Reference:

  1. Jean-Charles Lambert et al. Meta-analysis of 74,046 individuals identifies 11 new susceptibility loci for Alzheimer's disease. Nature Genetics, 2013; DOI: 10.1038/ng.2802

Cite This Page:

Boston University Medical Center. "Eleven new genetic susceptibility factors for Alzheimer's disease discovered through the largest study." ScienceDaily. ScienceDaily, 27 October 2013. <www.sciencedaily.com/releases/2013/10/131027185319.htm>.
Boston University Medical Center. (2013, October 27). Eleven new genetic susceptibility factors for Alzheimer's disease discovered through the largest study. ScienceDaily. Retrieved July 24, 2014 from www.sciencedaily.com/releases/2013/10/131027185319.htm
Boston University Medical Center. "Eleven new genetic susceptibility factors for Alzheimer's disease discovered through the largest study." ScienceDaily. www.sciencedaily.com/releases/2013/10/131027185319.htm (accessed July 24, 2014).

Share This




More Mind & Brain News

Thursday, July 24, 2014

Featured Research

from universities, journals, and other organizations


Featured Videos

from AP, Reuters, AFP, and other news services

New Painkiller Designed To Discourage Abuse: Will It Work?

New Painkiller Designed To Discourage Abuse: Will It Work?

Newsy (July 24, 2014) The FDA approved Targiniq ER on Wednesday, a painkiller designed to keep users from abusing it. Like any new medication, however, it has doubters. Video provided by Newsy
Powered by NewsLook.com
China's Ageing Millions Look Forward to Bleak Future

China's Ageing Millions Look Forward to Bleak Future

AFP (July 24, 2014) China's elderly population is expanding so quickly that children struggle to look after them, pushing them to do something unexpected in Chinese society- move their parents into a nursing home. Duration: 02:07 Video provided by AFP
Powered by NewsLook.com
Idaho Boy Helps Brother With Disabilities Complete Triathlon

Idaho Boy Helps Brother With Disabilities Complete Triathlon

Newsy (July 23, 2014) An 8-year-old boy helped his younger brother, who has a rare genetic condition that's confined him to a wheelchair, finish a triathlon. Video provided by Newsy
Powered by NewsLook.com
Huge Schizophrenia Study Finds Dozens Of New Genetic Causes

Huge Schizophrenia Study Finds Dozens Of New Genetic Causes

Newsy (July 22, 2014) The 83 new genetic markers could open dozens of new avenues for schizophrenia treatment research. 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