Loss of Y chromosome is a risk factor for Alzheimer’s disease: Why do men have shorter lives than women?



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Men with blood cells that do not carry the Y chromosome are at higher risk of being diagnosed with Alzheimer’s disease, and this is in addition to an increased risk of death from other causes, including many cancers,
Credit: © Jeremy Hiebert / Flickr

The loss of the Y chromosome in batches of blood cells over time continues to develop as one biological explanation for why men, on average, live shorter lives than women. Researchers reporting May 23, 2016 in the American Journal of Human Genetics found that men with blood samples showing loss of chromosome Y developed Alzheimer’s as often as people born with genes that put them at the most risk for the disease. The work will be presented at the annual conference of the European Society of Human Genetics.

“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,” says senior author Lars Forsberg, a researcher in the Department of Immunology, Genetics, and Pathology at Uppsala University in Sweden. “Using new tools to analyze genetic variations that accumulate with age, we can help explain how sporadic diseases like cancer or Alzheimer’s manifest,” says first author Jan Dumanski.
 


 
One such postzygotic mutation found in the cells of biological males is the loss of the Y chromosome in a degree of blood cells. Loss of Y occurs in up to 17 percent of men and is more likely to be found in older men and men who smoke. This study expands on the idea that loss of Y, already a known risk factor for cancer (10.1038/ng.2966), could be a predictive biomarker for a wider range of poor health outcomes, specifically Alzheimer’s. Why loss of Y can be linked to an increased risk for disease remains unclear, but the authors speculate it has to do with reduced immune system performance.

The researchers looked at over 3,000 men to ascertain whether there was any predictive association between loss of Y in blood cells and Alzheimer’s disease. The participants came from three long-term studies that could provide regular blood samples: the European Alzheimer’s Disease Initiative, the Uppsala Longitudinal Study of Adult Men, and the Prospective Investigation of the Vasculature in Uppsala Seniors. Across the datasets, those with the highest fraction of blood cells without a Y chromosome were consistently more likely to be diagnosed with Alzheimer’s.

“Having loss of Y is not 100 percent predictive that you will have either cancer or Alzheimer’s,” Forsberg says, adding that there were men in the study who had the mutation and lived with no symptoms well into their 90s. “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.”

Forsberg, Dumanski, and colleagues will next investigate the effect of loss of Y in larger cohorts and explore in greater detail how it confers risk for specific types of cancers and disease. They also plan to look at the cellular changes caused by loss of Y and how it affects different types of blood cells.

 


Source: Cell Press
Journal Reference:

  1. Dumanski et al. Mosaic loss of chromosome Y in blood is associated with Alzheimer’s disease. American Journal of Human Genetics, 2016 DOI: 10.1016/j.ajhg.2016.05.014
Posted in Health & Medicine on May 24, 2016