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Researchers identify new genetics risks for Alzheimer's disease

An International study examined the genome of more than 74,000 individuals

An international research consortium with the participation of the German Center for Neurodegenerative Diseases (DZNE) and the Bonn University Hospital has identified 11 previously unknown genetic risk factors for Alzheimer's disease.

The genome of over 25,000 patients as well as more than 48,000 healthy controls was analyzed to this end. The results have been published in the scientific journal “Nature Genetics”.

Alzheimer’s disease is a common cause of dementia. It is triggered by the death of brain cells and occurs in two variants: The so-called familial variant is relatively rare. It is caused by certain mutations in the genome and usually manifests itself already before the age of 65. However, more than 90 percent of the cases occur at an older age. The exact causes of this “sporadic” form of the disease are enigmatic. However, it is known that a disease may be favored by genetic traits, even though it may not necessarily be triggered by it.

So far, 11 such risk factors were known. A further 11 have now been identified by a team of researchers from the US and Europe. For this several universities and research institutions collaborated within the framework of the “International Genomics of Alzheimer's Project” (IGAP).

Large amounts of data

“Such an endeavor is enormously complex and requires the cooperation of many partners. We in particular contributed clinical data. This included anonymous genetic data of about one thousand patients that are diagnosed with Alzheimer’s disease,” says Dr. Alfredo Ramirez, who is a researcher at the Department of Psychiatry and Psychotherapy of Bonn University Hospital.

The memory clinic played an important role, explains Professor Frank Jessen, who is Deputy Director of the Department of Psychiatry and Psychotherapy and also a researcher affiliated to the DZNE: “Longtime preparations are needed for such a study. On the basis of our memory clinic we have been in touch with people diagnosed with memory disorders for many years. Through this we have been able to build up an extensive repository of genetic data from patients. We made this data available for the study.”

“In the case of such genetic studies, it is ultimately a matter of comparing the genomes of patients and controls,” explains Dr. Tim Becker from the Bonn site of the DZNE. Within the framework of the now published study he focused in particular on the analysis of genetic data. “We searched for genetic traits that are prevalent in persons that have been diagnosed with the disease. In order to do so, genetic data from many people has to be compared. This is the only way to obtain meaningful results and to distinguish random signals from real findings.”

Important contributions also came from the Institute of Human Genetics of the Bonn University Hospital. “We genotyped samples of DNA. This is very similar to doing genetic fingerprinting,” says Professor Markus Nöthen, head of the Institute.

Screening the genome

The IGAP consortium studied the genome of a total of 74,046 people. Of these, more than 25,000 were diagnosed with Alzheimer’s disease, the others were controls. High performance computing assisted in the analysis of the huge amount of data.

Pivotal to the research were so-called genome-wide association studies (GWAS). The genome, with its billions of building blocks, was thereby not fully cataloged, but instead only examined at relevant positions. This type of screening saves time and money, while at the same time providing a good coverage. The researchers examined about seven million positions.

Critical positions

“We identified eleven positions in the human genome that were previously largely ignored. However, if certain alterations are present there, the probability of developing Alzheimer’s increases,” says Becker. “Yet, this increased risk does not necessarily lead to disease.”

So far the researchers do not yet know in detail what role the affected regions play. “Some of these genes are related to Amyloid-beta and tau proteins that are known to be relevant for the Alzheimer’s disease. With regard to the other critical regions, we can not say with certainty what role they play”, says Ramirez. “We assume that they have an effect, for example, on nervous connections and on transport processes occurring inside the nerve cells. In addition, the immune system seems to be involved. As a next step, it will be important to investigate this in more detail.”

Original publication
“Meta-analysis of 74,046 individuals identifies 11 new susceptibility loci for Alzheimer’s disease”, Nature Genetics, published online on October 27, 2013,

Dr. Marcus Neitzert | idw
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