Men lost the Y chromosome in a proportion of their blood cells are at greater risk of developing Alzheimer’s disease, except that they also have a greater risk of dying from other causes, including several forms of cancer. The researchers at Uppsala University in a new study, the results of which can lead to the development of a simple test to identify those at risk of getting Alzheimer’s disease.
The results are published today in the American Journal of Human Genetics.
The loss of the Y chromosome in a proportion of blood cells (which are called LOY) occurs in approximately 20 percent of all men over 80 years of age and it is the most common genetic deviation that occur during a man’s life.
Lars Forsberg and Jan Dumanski, a researcher at the Department of Immunology, Genetics and Pathology at Uppsala University, together with colleagues from Sweden, France, UK, USA and Canada, investigated the loss of the Y chromosome of over 3200 men aged 37-96 years, with an average age of 73 years. About 17 percent of them showed LOY in blood cells and the percentage increased with age. The researchers discovered that men who had been diagnosed with Alzheimer’s disease had a higher proportion of cells with LOY and that the loss of the Y chromosome was a marker for the likelihood of developing the disease during the follow up period.
– I got the idea for this project when I wrote our first article on the relationship between the loss of the Y chromosome and the development of cancer. When I thought about the process called immune surveillance, that is, the immune system’s ability to throughout their lives fighting the appearance of diseases, I saw that it is something that has been widely studied for Alzheimer’s disease, and it struck me that LOY could be involved even in this disease, says Lars Forsberg.
Since women have no Y chromosome, and men on average have shorter life span, it is possible to LOY may have a connection with men die earlier. However, the researchers emphasize, the mechanisms and reasons behind their findings is not yet clear. They are currently investigating the effect of the loss of the Y chromosome and the importance of different groups of men and in other diseases, to better understand the types of cancer that may be linked to LOY. They also want to find out if there is any connection to the early signs of dementia such as lighter cognitive impairment.
Other issues that need to be answered is whether the loss of the Y chromosome in the blood cells have no relation to diseases in other organ.
– The blood cells that we have studied belong to the immune system and it is noteworthy that loss of the Y chromosome in the cells can be linked to diseases of other tissues. Our hypothesis is that it is the loss of the Y chromosome that causes cells to lose a part of the function of the immune system, says Jan Dumanksi.
Earlier results from the same research group has shown that smoking increases the risk of losing Y- chromosome in blood cells by as much as 400 percent. However, smoking seems to have a temporary impact and be dose-dependent, so if you stop smoking, the effect return. It is something one should emphasize the anti-rökkampanjer the researchers.
A more difficult question is whether the diagnosis and treatment of serious conditions such as Alzheimer’s disease and cancer. Today, based on the identification of clinical symptoms and the development of diagnostic methods for early detection can lead to strategies for preventing diseases arise even before clinical symptoms develop. In the future, it would for example be possible to use a test for the loss of the Y chromosome to identify men with higher risk and then do oncological or neurological examinations to find early, mild symptoms of illness. LOY can also become an important diagnostic tool in conjunction with other biomarkers that can be used to predict the risk of various diseases.
– A general test of the loss of the Y chromosome in the population would give doctors opportunities to take preventative measures for men with higher risk. In cancer, for example the primary tumor is often not fatal, it is the spread of metastasis that results in death. If one can predict which men who have a higher risk of getting cancer, they could be monitored more carefully to discover if the disease occurs and you would start preventive treatment. As a general test of the loss of the Y chromosome could lower the mortality of male radical and perhaps even smooth out the difference in life expectancy between men and women, says Lars Forsberg.
for more information, please contact:
January Dumanksi; jan.dumanski@igp.uu.se, office: +46 18 471 5035, mobile: +46 70 4250616
Lars Forsberg; lars.forsberg@igp.uu.se
Article:
Mosaic loss of the Y chromosome in blood is Associated with Alzheimer’s disease, the American Journal of Human Genetics, DOI: 10.1016/j.ajhg.2016.05.014.
http://www.cell.com/ajhg/fulltext/S0002-9297(16)30149-5.
Forskarna the study linked to the Science for Life Laboratory (SciLifeLab). SciLifeLab is a national center for molecular biosciences focusing on research in health and environment. The center combines technical expertise and advanced instruments with a broad expertise in translational medicine and molecular life sciences.
Uppsala University – quality, knowledge, and creativity since 1477. world-class research and outstanding education of global benefit to society, business and culture. Uppsala University is one of Northern Europe’s highest ranked universities. www.uu.se
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