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Age-Related Y Chromosome Loss and Alzheimer's Risk

In recent years researchers have noted that a small proportion of cells in males lose their Y chromosome over the course of aging. This appears to correlate with mortality and cancer risk, among other things, though there is no good picture of why this is the case at the present time. Aging is a global phenomenon, occurring in all tissues and organs, and so most aspects of aging correlate with one another, making it challenging to pick out cause and effect. Here, researchers find a correlation between Y chromosome loss and risk of suffering Alzheimer's disease:

"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. Using new tools to analyze genetic variations that accumulate with age, we can help explain how sporadic diseases like cancer or Alzheimer's manifest." 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, 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, as 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." The researchers 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.

Link: http://www.eurekalert.org/pub_releases/2016-05/cp-loy051816.php

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