Men who are missing the Y chromosome in their blood cells are at increased risk of developing Alzheimer’s disease, a new Swedish study has revealed.
And the Alzheimer’s risk is in addition to an increased risk of death from other causes, including many cancers, the annual conference of the European Society of Human Genetics will hear today (24 May, 2016).
Professors Lars Forsberg and Jan Dumanski, from the Department of Immunology, Genetics and Pathology, Uppsala University, will say they hope their findings will lead to the creation of a simple test that will enable medics to identify those at risk of developing the disease.
The loss of the Y chromosome (LOY) affects up to 20% of men over the age of 80 and their study included more than 3,200 men, whose ages ranged from 37-96. Of these, about 17% had LOY and this increased with age. However, the men with an existing diagnosis of Alzheimer’s disease had a higher degree of LOY, and that LOY was also a marker for the likelihood of developing the disease during the follow-up period.
“Most genetic research today is focused on inherited gene variants – mutations that are inherited by the offspring, but what we’re looking at are postzygotic mutations that are acquired during life,” said senior author Professor Forsberg, whose study is published today in the American Journal of Human Genetics.
“Having loss of Y is not 100% predictive that you will have either cancer or Alzheimer’s, but in the future, loss of Y in blood cells can become a new biomarker for disease risk and perhaps evaluation can make a difference in detecting and treating problems early.”
First author Professor Dumanski added: “Using new tools to analyse genetic variations that accumulate with age, we can help explain how sporadic diseases like cancer or Alzheimer’s manifest.”
Because women do not carry a Y chromosome, and men’s life expectancy is, on average, shorter, LOY could be linked to men’s earlier death. But the mechanisms and causes for their findings are still not properly understood.
The team, which also includes researchers from France, USA, Canada, Sweden, and the UK, are investigating the functional effects of LOY, and looking at its role men and in diseases to understand which types of cancer are associated with LOY, and to establish if there is a link with early signs of dementia.
“The blood cells we studied are involved in the immune system, and the fact that LOY in them is associated with disease in other tissues is striking,” said Professor Dumanski. “We therefore hypothesise that the loss of LOY in blood cells leads them to lose part of their immune function.”
Although previous research by the same group demonstrated that smoking increases the risk of LOY by up to 400%, which can be reversed by quitting the habit, it is more difficult to diagnosis and treatment of serious conditions such as AD and cancer.
The development of diagnostic tools for earlier detection could lead to strategies that aim to prevent the progress of the disease before symptoms occur.
Forsberg L, Dumanski J et al. Mosaic loss of chromosome Y in blood is associated with Alzheimer’s disease. American Journal of Human Genetics 24 May 2016; doi: 10.1016/j.ajhg.2016.05.014.
Leave a Reply