A recent study published in the American Journal of Human Genetics suggests that men who lose their Y-chromosome may gain a rather unfortunate side-effect: An increased risk of the neurodegenerative condition Alzheimer’s disease (AD).

The authors analyzed data from three previous long-running population studies of men over the age of 65. The studies allowed them to look for a genetic mutation in the men’s blood cells — the loss of the Y chromosome (LOY). From there, they found that men with Alzheimer’s had a greater degree of LOY than those without the condition and that men who had LOY at the beginning of the study were more likely to eventually develop Alzheimer’s. Coupled with earlier research of theirs showing a similar connection with certain cancers, the researchers theorize that men’s loss of the Y chromosome may even help solve an enduring mystery of the debilitating neurodegenerative disease.

“[I]t has been known for centuries that men have a shorter life expectancy compared to women, even in regions of the world with well-developed healthcare, but the underlying factor(s) behind this sex difference are not clear,” the study's researchers wrote. “Mosaic LOY in blood, being a male-specific risk factor for both AD and cancer, might at least partly explain why men on average live shorter than women.”

The Y chromosome is most well-known for being an influential factor in determining the genetic sex of a newly conceived embryo. The typical healthy human being has 23 pairs of chromosomes, 22 of which are nearly identical among healthy individuals. The remaining pair, however, is typically either XX or XY, with the Y chromosome specifically containing certain genes responsible for producing male sex organs. But the Y chromosome also has other genes that have nothing to do with determining sex. Many of these genes can be found elsewhere in women, but others are exclusively found only in those who possess the Y chromosome.

The LOY mutation, defined as having 10 percent or more blood cells without the Y chromosome, is fairly common in men, especially as they age. At least 15 percent of men over the age of 70 have that degree of LOY, according to research cited by the authors. However, until recently the mutation was seen as an ordinary part of aging, with little to no health consequences.

Though the current study can’t explain why this connection exists, the authors do have a leading theory. “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 lead author Jan Dumanski, a professor in the Department of Immunology, Genetics and Pathology at Uppsala University in Sweden, in a statement. “We therefore hypothesize that the loss of LOY in blood cells leads them to lose part of their immune function.”

Intriguing as the findings are, though, other experts note that it’s far too soon to jump to any conclusions about the exact role the Y chromosome may play in men’s Alzheimer's risk.

“The Y chromosome could be important for many quantitative traits, in addition to male sex determination and sperm production. There are reports of both Y-located cancer-causing genes and tumor suppressors,” Dr. Chris Lau, a professor in the Department of Medicine at the University of California, San Francisco, told Genetic Expert News Service. “However, it is doubtful that loss of Y alone can be used as a predictive biomarker for Alzheimer’s disease and cancer.”

Cancer and Alzheimer’s disease are complicated conditions, with many different risk factors and causes that interact with one another in a variety of ways. Similarly, even if LOY is confirmed to be connected to these conditions, it’s known that having a Y chromosome also increases the risk of developing other conditions like autism. So it’s unlikely that LOY alone can explain why men’s lives are shorter than women’s, Lau added.

It seems that only more research will be able to illuminate just how harmful the loss of the Y chromosome could be to aging men.

Source: Dumanski J, Lambert J-C, Rasi C, et al. Mosaic Loss of Chromosome Y in Blood Is Associated with Alzheimer Disease. American Journal of Human Genetics. 2016.