Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

International collaboration finds 11 new Alzheimer's genes to target for drug discovery

28.10.2013
Study yields fresh look at role of immune system in Alzheimer's

University of Miami Miller School of Medicine researchers played a key role in the largest international Alzheimer's disease genetics collaboration to date, which identified 11 new regions of the genome that contribute to late-onset Alzheimer's disease, doubling the number of potential genetics-based therapeutic targets to investigate.

Published October 27 in Nature Genetics, the study gives a broader view of the genetic factors contributing to Alzheimer's and expands the understanding of the disease to new areas, including the immune system, where a genetic overlap with other neurodegenerative diseases, including multiple sclerosis and Parkinson's disease, was identified.

In 2011, the world's four largest research consortia on the genetics of Alzheimer's disease joined efforts to discover and map the genes that contribute to Alzheimer's, forming the International Genomics of Alzheimer's Project (IGAP). The team collected genetic information from 25,500 Alzheimer's disease patients and 49,038 controls from 15 countries to perform this two-stage meta-analysis that resulted in the discovery of 11 new genes in addition to those already known, and the identification of 13 other genes, yet to be validated.

Margaret A. Pericak-Vance, Ph.D., the Dr. John T. Macdonald Foundation Professor of Human Genomics and Director of the John P. Hussman Institute for Human Genomics at the Miller School, and Lindsay A. Farrer, Ph.D., from Boston University, led the analysis teams for the American Alzheimer's Disease Genetics Consortium, which includes nearly all of the nation's researchers working on the genetics of Alzheimer's, as well as many investigators and resources of the 29 federally funded Alzheimer's Disease Centers.

Several of the genes the researchers identified confirmed known biological pathways of Alzheimer's disease, including the role of the amyloid (SORL1, CASS4) and tau (CASS4, FERMT2) pathways. Newly discovered genes involved in the immune response and inflammation (HLA-DRB5/DRB1, INPP5D, MEF2C) reinforced a pathway implied by previous work (on CR1, TREM2). Additional genes related to cell migration (PTK2B), lipid transport and endocytosis (SORL1) also were confirmed, and new hypotheses 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).

One of the more significant new associations was found in the HLA-DRB5/DRB1 region, one of the most complex parts of the genome, which plays a role in the immune system and inflammatory response. It also has been associated with multiple sclerosis and Parkinson's disease, suggesting that the diseases where abnormal proteins accumulate in the brain may have a common mechanism involved, and possibly a common drug target.

"The discovery of novel pathways is very encouraging considering the limited success of Alzheimer's disease drugs tested so far," Pericak-Vance said. "Our findings bring us closer toward identifying new drug targets for Alzheimer's and other neurodegenerative diseases. We'll continue to expand and analyze our data set with this incredible group so that we can better understand the genetic influences on this devastating disease, and find new medical and therapeutic interventions."

Other Miller School co-authors include the Hussman Institute's Gary Beecham, Ph.D., assistant professor of human genetics; Eden R. Martin, Ph.D., professor of human genetics; John R. Gilbert, Ph.D., professor of human genetics; Kara Hamilton-Nelson, M.S., project manager for research support; and Brian Kunkle, Ph.D., postdoctoral associate; and Amanda Meyers, Ph.D., associate professor of psychiatry and behavioral sciences.

The IGAP includes contributions from the Alzheimer's Disease Genetics Consortium (ADGC) in the United States, which is led by Gerard Schellenberg, Ph.D., Perelman School of Medicine at the University of Pennsylvania; the European Alzheimer's Disease Initiative in France, led by Philippe Amouyel, M.D., Ph.D., at the Institute Pasteur de Lille and Lille University; the Genetic and Environmental Risk in Alzheimer's Disease from the United Kingdom, led by Julie Williams, Ph.D., at Cardiff University; the neurology subgroup of the Cohorts for Heart and Aging in Genomic Epidemiology, led by Sudha Seshadri, M.D., at Boston University School of Medicine; as well as teams from the University of Miami, Vanderbilt University, and Columbia University in the United States, among others.

Alexandra Bassil | EurekAlert!
Further information:
http://www.miami.edu

More articles from Life Sciences:

nachricht Multi-institutional collaboration uncovers how molecular machines assemble
02.12.2016 | Salk Institute

nachricht Fertilized egg cells trigger and monitor loss of sperm’s epigenetic memory
02.12.2016 | IMBA - Institut für Molekulare Biotechnologie der Österreichischen Akademie der Wissenschaften GmbH

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

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

Im Focus: Novel silicon etching technique crafts 3-D gradient refractive index micro-optics

A multi-institutional research collaboration has created a novel approach for fabricating three-dimensional micro-optics through the shape-defined formation of porous silicon (PSi), with broad impacts in integrated optoelectronics, imaging, and photovoltaics.

Working with colleagues at Stanford and The Dow Chemical Company, researchers at the University of Illinois at Urbana-Champaign fabricated 3-D birefringent...

Im Focus: Quantum Particles Form Droplets

In experiments with magnetic atoms conducted at extremely low temperatures, scientists have demonstrated a unique phase of matter: The atoms form a new type of quantum liquid or quantum droplet state. These so called quantum droplets may preserve their form in absence of external confinement because of quantum effects. The joint team of experimental physicists from Innsbruck and theoretical physicists from Hannover report on their findings in the journal Physical Review X.

“Our Quantum droplets are in the gas phase but they still drop like a rock,” explains experimental physicist Francesca Ferlaino when talking about the...

Im Focus: MADMAX: Max Planck Institute for Physics takes up axion research

The Max Planck Institute for Physics (MPP) is opening up a new research field. A workshop from November 21 - 22, 2016 will mark the start of activities for an innovative axion experiment. Axions are still only purely hypothetical particles. Their detection could solve two fundamental problems in particle physics: What dark matter consists of and why it has not yet been possible to directly observe a CP violation for the strong interaction.

The “MADMAX” project is the MPP’s commitment to axion research. Axions are so far only a theoretical prediction and are difficult to detect: on the one hand,...

Im Focus: Molecules change shape when wet

Broadband rotational spectroscopy unravels structural reshaping of isolated molecules in the gas phase to accommodate water

In two recent publications in the Journal of Chemical Physics and in the Journal of Physical Chemistry Letters, researchers around Melanie Schnell from the Max...

Im Focus: Fraunhofer ISE Develops Highly Compact, High Frequency DC/DC Converter for Aviation

The efficiency of power electronic systems is not solely dependent on electrical efficiency but also on weight, for example, in mobile systems. When the weight of relevant components and devices in airplanes, for instance, is reduced, fuel savings can be achieved and correspondingly greenhouse gas emissions decreased. New materials and components based on gallium nitride (GaN) can help to reduce weight and increase the efficiency. With these new materials, power electronic switches can be operated at higher switching frequency, resulting in higher power density and lower material costs.

Researchers at the Fraunhofer Institute for Solar Energy Systems ISE together with partners have investigated how these materials can be used to make power...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

ICTM Conference 2017: Production technology for turbomachine manufacturing of the future

16.11.2016 | Event News

Innovation Day Laser Technology – Laser Additive Manufacturing

01.11.2016 | Event News

#IC2S2: When Social Science meets Computer Science - GESIS will host the IC2S2 conference 2017

14.10.2016 | Event News

 
Latest News

UTSA study describes new minimally invasive device to treat cancer and other illnesses

02.12.2016 | Medical Engineering

Plasma-zapping process could yield trans fat-free soybean oil product

02.12.2016 | Agricultural and Forestry Science

What do Netflix, Google and planetary systems have in common?

02.12.2016 | Physics and Astronomy

VideoLinks
B2B-VideoLinks
More VideoLinks >>>