The genes were discovered following the most comprehensive work of comparing the genomes of 74 thousand people - sick and healthy in 15 countries
The largest international study ever conducted in Alzheimer's disease carried out by a consortium of researchers specially established I-GAP (International Genomics Alzheimer's Project) resulted in the discovery of 11 new regions in the genome involved in the onset of the degenerative disease.
This study provides an overview of the molecular mechanisms underlying Alzheimer's disease, and may open a door to a better understanding of the pathophysiology of the sequence. The results of the research, which could not have been achieved without the joint effort of scientists from all over the world, were published in the journal Nature Genetics.
Since 2009, 10 genes associated with Alzheimer's disease have been identified, however, a significant proportion of susceptibility factors that cause a person to develop the disease remain unexplained. In February 2011, the largest international association was established whose purpose was to speed up the discovery of new genes. The association is supported in part by the National Institute on Aging (NIA) and other institutes that are members of the National Institutes of Health (NIH).
In less than three years, the IGAP program identified more genes than the number of genes identified during the previous 20 years. They collected genetic data on 74,076 people - some sick and the others healthy who served as a control group from 15 countries and managed to identify 11 new genes in addition to the known ones. 13 more genes were also discovered but these have not yet been verified.
The 11 newly approved genes may open new avenues for understanding the causes of the disease. For example, one of the most significant concentrations is found in the major histocompatibility complex in the HLA-DRB5/DRB1 region. This finding is interesting in several ways. First, it indicates the involvement of the immune system in the disease. In addition, the same area is also associated with two other degenerative diseases: one - multiple sclerosis is known for its connection to the immune system. And the second is Parkinson's disease.
Some of the confirmed genes strengthen biological pathways known to be involved in Alzheimer's, 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 strengthened, as is the importance of cell migration (PTK2B), lipid transport in the brain and endocytosis (SORL1).
New hypotheses were also put forward for the synaptic function in the hippocampus (MEF2C, PTK2B), the cell skeleton and axon transport (CELF1, NME8, CASS4). as well as myeloid and microglial cell functions (INPP5D).
Finally, this work proves that, given the complexity of such a disease, only a global collaboration of researchers in a joint research effort can help quickly find solutions to deal with this major threat.
"This study clearly demonstrates that there really is power in a large number of researchers to identify genes that have a small effect on individual Alzheimer's risk," says Dr. Lindsay Farrer of Boston University. But adding each gene to the complex of the disease can provide insight into the development of new therapeutic approaches that may be more effective in the younger stage of the disease, because these genes can be located long before clinical symptoms appear and brain damage occurs."
