Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

New gene uncovered for late-onset Alzheimer's

17.01.2007
Findings replicated in four different ethnic groups: Caribbean-Hispanics, Northern Europeans, African-Americans and Israeli-Arabs

An international team of researchers, led by Columbia University Medical Center, Boston University School of Medicine and the University of Toronto, has uncovered a major new gene -- SORL1 -- implicated in late-onset Alzheimer's disease. Replicated in four distinct ethnic groups, SORL1 is only the second genetic variant for late-onset Alzheimer's, the type of Alzheimer's found in 90 percent of people with this devastating disease. ApoE4, the first, was identified in 1993.

In an article published in the Jan. 14 advance on-line edition of Nature Genetics (February print edition), researchers describe how variants in the SORL1 gene were found to be more common in people with late-onset Alzheimer's than in healthy people the same age. The authors believe that these genetic variants alter the normal function of SORL1, sending amyloid precursor protein (APP) down a pathway that increases the production of the toxic amyloid beta (A£]) peptides in the brain resulting in Alzheimer's. When the SORL1 gene works properly, it sends APP along recycling pathways -- preventing it from being cut into toxic A£] forms.

People with these genetic variants may not produce normal amounts of SORL1, suggesting that this gene has protective function when working properly. The researchers believe that the reduction of SORL1 in the brain increases the likelihood of developing Alzheimer's disease.

An important aspect of their findings was that the association between Alzheimer's disease and SORL1 was replicated in four distinct ethnic groups: Caribbean-Hispanics, North Europeans, African-Americans and Israeli-Arabs. Many previous studies on the genetics of Alzheimer's used data from mostly white populations of American and European ancestry. In total, the five-year federally- and internationally-funded study involved DNA samples from 6,000 volunteers.

The research team at Columbia University Medical Center was led by Richard Mayeux, M.D., co-director of the Taub Institute for Research on Alzheimer's Disease and the Aging Brain. The team at the University of Toronto was led by Peter St. George-Hyslop, M.D., director of the Centre for Research in Neurodegenerative Diseases, and the Boston University team by Lindsay Farrer, Ph.D., chief of the Genetics Program. Steven Younkin, M.D., Ph.D., chair of Department of Pharmacology at the Mayo Clinic College of Medicine in Jacksonville, Fla. also provided DNA samples from the Mayo's respective unique populations for the study.

"The importance of the finding is that it opens new pathways to explore the cause and as well as potential targets for treatment of this devastating disease," said Dr. Mayeux. "SORL1 represents another critical piece of the Alzheimer's disease puzzle. This appears to be the fifth Alzheimer's disease gene, and there are likely to be other important genetic variants that need to be identified before the entire picture is complete."

"Instead of scanning all the genes in the entire genome, we had an idea of what an Alzheimer's disease-causing gene would look like based on past discoveries," said Dr. St. George-Hyslop. "We knew that the abnormalities in APP processing and the accumulation of its toxic amyloid beta (AƒÒ) peptide derivative cause Alzheimer's, so we hypothesized that other genes associated with APP regulation might also cause the disease."

Genetic Homogeneity of Dominican Population Tapped for Discovery

In 1994, Dr. Mayeux noticed, upon studying elderly residents of Washington Heights, a predominantly Hispanic neighborhood in Northern Manhattan where Columbia University Medical Center is located, that Dominicans have about three times the rate of Alzheimer's disease compared to individuals of different ethnic backgrounds in the community. Dr. Mayeux decided to find out why this population has such a high incidence of Alzheimer's, so he and his Columbia team began visiting Dominican families living in both Washington Heights and the Dominican Republic to collect blood samples of entire families in order to look for similar gene variations in relatives diagnosed with Alzheimer's.

"The Dominican population is very concerned about the increased frequency of disease and was very helpful in forming the basis of this study. From a genetic perspective, Dominicans are a relatively homogenous population, and follow similar diet and living patterns," said Dr. Mayeux. "Because individuals within families stay in touch and remain close to one another even after migrating to the United States, we were able to identify families in this large population that were very similar genetically."

To confirm their preliminary findings, Drs. Mayeux and St. George-Hyslop, his collaborator of more than 25 years, reached out to other colleagues who tapped genetic records of people of from even more diverse ethnic backgrounds.

In total, the initial discovery group included 350 families (representing a total of 1,800 people, half of whom had Alzheimer's), from Columbia University Medical Center and the University of Toronto. The group was divided into two parts: one that was analyzed to help with the discovery of SORL1, and a second that was analyzed to confirm the role of the gene. To this collection, Dr. Farrer, from Boston University School of Medicine, added 500 African-American sibling pairs (representing a total of 1,000 people), where one sibling was diagnosed with Alzheimer's and the other was not. Farrer also enabled the researchers to reconfirm their findings in an examination of data from Israeli-Arabs, while Younkin's data from mostly white Alzheimer's patients provided by the Mayo Clinic also confirmed the findings. Interestingly, the same variant was found in both the Israeli-Arab and Caribbean-Hispanic groups, which indicates that generations ago these two groups may have been genetically or geographically linked.

Seeking Pathogenesis of SORL1 & Attributable Risk of SORL1 Variants

"Now that we know that variants in SORL1 are associated with late-onset Alzheimer's disease and we know the specific regions of the gene involved, our next step is to determine which of the variants contain the specific disease causing alteration," said Dr. Mayeux.

Another next step is to determine how many cases of late-onset Alzheimer's are caused by these SORL1 variants; it is known that ApoE4 explains approximately 20 percent of all cases of late-onset Alzheimer's. Studies are planned to investigate how many Alzheimer's cases are attributable to SORL1. The hope is that this information will help develop accurate screening for this gene.

Elizabeth Streich | EurekAlert!
Further information:
http://www.columbia.edu

Further reports about: APP African-American Caribbean-Hispanic Dominican Israeli-Arab Mayeux SORL1 late-onset

More articles from Life Sciences:

nachricht Nanoparticle Exposure Can Awaken Dormant Viruses in the Lungs
16.01.2017 | Helmholtz Zentrum München - Deutsches Forschungszentrum für Gesundheit und Umwelt

nachricht Cholera bacteria infect more effectively with a simple twist of shape
13.01.2017 | Princeton University

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

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

Im Focus: Interfacial Superconductivity: Magnetic and superconducting order revealed simultaneously

Researchers from the University of Hamburg in Germany, in collaboration with colleagues from the University of Aarhus in Denmark, have synthesized a new superconducting material by growing a few layers of an antiferromagnetic transition-metal chalcogenide on a bismuth-based topological insulator, both being non-superconducting materials.

While superconductivity and magnetism are generally believed to be mutually exclusive, surprisingly, in this new material, superconducting correlations...

Im Focus: Studying fundamental particles in materials

Laser-driving of semimetals allows creating novel quasiparticle states within condensed matter systems and switching between different states on ultrafast time scales

Studying properties of fundamental particles in condensed matter systems is a promising approach to quantum field theory. Quasiparticles offer the opportunity...

Im Focus: Designing Architecture with Solar Building Envelopes

Among the general public, solar thermal energy is currently associated with dark blue, rectangular collectors on building roofs. Technologies are needed for aesthetically high quality architecture which offer the architect more room for manoeuvre when it comes to low- and plus-energy buildings. With the “ArKol” project, researchers at Fraunhofer ISE together with partners are currently developing two façade collectors for solar thermal energy generation, which permit a high degree of design flexibility: a strip collector for opaque façade sections and a solar thermal blind for transparent sections. The current state of the two developments will be presented at the BAU 2017 trade fair.

As part of the “ArKol – development of architecturally highly integrated façade collectors with heat pipes” project, Fraunhofer ISE together with its partners...

Im Focus: How to inflate a hardened concrete shell with a weight of 80 t

At TU Wien, an alternative for resource intensive formwork for the construction of concrete domes was developed. It is now used in a test dome for the Austrian Federal Railways Infrastructure (ÖBB Infrastruktur).

Concrete shells are efficient structures, but not very resource efficient. The formwork for the construction of concrete domes alone requires a high amount of...

Im Focus: Bacterial Pac Man molecule snaps at sugar

Many pathogens use certain sugar compounds from their host to help conceal themselves against the immune system. Scientists at the University of Bonn have now, in cooperation with researchers at the University of York in the United Kingdom, analyzed the dynamics of a bacterial molecule that is involved in this process. They demonstrate that the protein grabs onto the sugar molecule with a Pac Man-like chewing motion and holds it until it can be used. Their results could help design therapeutics that could make the protein poorer at grabbing and holding and hence compromise the pathogen in the host. The study has now been published in “Biophysical Journal”.

The cells of the mouth, nose and intestinal mucosa produce large quantities of a chemical called sialic acid. Many bacteria possess a special transport system...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

12V, 48V, high-voltage – trends in E/E automotive architecture

10.01.2017 | Event News

2nd Conference on Non-Textual Information on 10 and 11 May 2017 in Hannover

09.01.2017 | Event News

Nothing will happen without batteries making it happen!

05.01.2017 | Event News

 
Latest News

Water - as the underlying driver of the Earth’s carbon cycle

17.01.2017 | Earth Sciences

Interfacial Superconductivity: Magnetic and superconducting order revealed simultaneously

17.01.2017 | Materials Sciences

Smart homes will “LISTEN” to your voice

17.01.2017 | Architecture and Construction

VideoLinks
B2B-VideoLinks
More VideoLinks >>>