International research team discovers new Alzheimer's gene
16.11.2012 17:49
An international team of Alzheimer's researchers has carried out extensive genome analyzes and found a new gene variant that, although rare, is associated with a significantly increased risk of Alzheimer's disease. The current findings primarily support a number of previous study results, according to which inflammatory processes play an essential role in the pathogenesis of the disease.
The work shows - in agreement with other study data - that it certainly makes sense to take inflammatory processes in the brain into account both in the search for further diagnostic indicators, i.e. biomarkers, and new Alzheimer's therapies, says Harald Hampel (University of Frankfurt am Main). , one of the scientists involved in the current genome study. The work of the team led by Professors Hampel and Kári Stefánsson, head of the Icelandic company “Decode Genetics”, has just been published in the renowned “New England Journal of Medicine”.
The new risk factor is a variant of a gene that contains the instructions for a special cell receptor (TREM2). In the brain, the receptor is found primarily on microglial cells, which, when activated, are involved in the phagocytosis of cell waste and also amyloid. Microglial cells can also promote the production of proinflammatory cytokines (such as tumor necrosis factor) or develop into antigen-presenting cells, potentially triggering an immune response.
The gene variant is based on a point mutation that leads to an exchange of the amino acids histidine and arginine in the gene product. Since the physiological receptor TREM2 is involved in the phagocytosis of, among other things, toxic amyloid plaques, it may be that the genetically defective receptor results in impaired removal of such neurotoxic products.
According to the researchers, the risk allele (rs75932628-T) is very rare (0.63 percent in the Icelandic study population); However, as the comparison with non-carriers who are at least 85 years old showed, carriers of this allele have an increased risk of Alzheimer's disease by a factor of 2.92. This increase in risk roughly corresponds to that associated with the ApoE-e4 allele, which is known as a risk factor (factor 3.08). However, its frequency in the Icelandic population is significantly higher at around 17 percent.
Further calculations by the team also provided evidence that people with the new gene variant develop Alzheimer's disease earlier than non-carriers. In addition, the analyzes showed that the cognitive performance of 80 to 100-year-old carriers of the allele was worse than that of non-carriers of the same age, report the authors, whose work is supported by the “National Institute on Aging” and other institutions including the EU Commission was supported.
Harald Hampel and his colleagues reported last year in the journal “Nature Genetics” that inflammatory and immunological processes play a significant role in the development of Alzheimer’s disease. In their analysis of the genomes of almost 60,000 people (almost 20,000 Alzheimer's patients), the researchers found five risk genes (ABCA7, MS4A, EPHA1, CD33, CD2AP), whose protein products are, among other things, involved in cellular transport processes the regulation of inflammatory and immunological processes and also fat metabolism. The current genome analysis is the continuation of previous genome analyzes - with the medium-term goal of describing the entire genetic profile of Alzheimer's disease.
Original work: Thorlakur Jonsson et. al.: Variant of TREM2 Associated with the Risk of Alzheimer's Disease. N Engl J Med 2012; 14th November; DOI: 10.1056/NEJMoa11211103