Loss of the Y chromosome in blood cells puts men at the same risk of developing Alzheimer’s disease as individuals carrying familial high-risk mutations, offering a new marker for assessing disease risk, also including other age-related diseases, such as cancer.
Partial loss of the Y chromosome over time, present in 17 percent of men, has already been proposed as an explanation of why men live shorter lives than women, and is linked to cancer and other life-threatening diseases. This so-called postzygotic mutation — meaning it is not inherited — is more often found in older men, as well as in men who smoke.
“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,” senior study author Lars Forsberg, a researcher in the Department of Immunology, Genetics, and Pathology at Uppsala University in Sweden, said in a news release.
The study, “Mosaic Loss of Chromosome Y in Blood Is Associated with Alzheimer Disease,” published in the American Journal of Human Genetics, investigated the risk for Alzheimer’s in more than 3,000 men already enrolled in studies that provided access to 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.
In all three groups of men, the researchers found that higher proportions of blood cells lacking the Y chromosome predicted the development of Alzheimer’s. Still, the prediction was not foolproof, as the study found men with the mutation who lived a healthy life until old age. Researchers also don’t know why the loss of Y puts men at increased risk for Alzheimer’s, but they speculated that reduced immune processes might be involved.
“Using new tools to analyze genetic variations that accumulate with age, we can help explain how sporadic diseases like cancer or Alzheimer’s manifest,” said first author Jan Dumanski.
“Having loss of Y is not 100 percent predictive that you will have either cancer or Alzheimer’s,” Forsberg said. “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.”