Alzheimer’s linked to loss of Y chromosome in men

New research, presented this week at the European Society of Human Genetics conference in Barcelona, Spain, demonstrates that men whose red blood cells lack Y chromosomes are more susceptible to Alzheimer’s disease. The team hopes that, in the future, these findings might help develop an early warning system for Alzheimer’s.
[Old man looking out of window]
Could the percentage of cells lacking a Y chromosome predict disease outcomes in men?

Alzheimer’s disease affects more than 5 million Americans; that equates to 1 in 9 people over the age of 65.

By 2050, the number of individuals with the condition is predicted to rise to 14 million.

Despite the huge number of Alzheimer’s cases, the molecular mechanisms behind it and the exact risk factors are still poorly understood.

The primary risk factor for Alzheimer’s disease is advanced age, but there do seem to be other parameters involved.

For instance, there appears to be a genetic susceptibility. Other researchers have investigated links between Alzheimer’s and high blood pressure, low folate intake, and high cholesterol levels; levels of mental and physical activity are also thought to play a role.

Recent research, examining an unusual but prevalent genetic change in men, may have unearthed a new clue to the etiology of Alzheimer’s.

Loss of Y chromosome

Females have two X chromosomes, while men have one X and one Y. Among other things, the Y chromosome contains code that triggers the development of the testis.

Over recent years, it has been noted that in some men, the Y chromosome slowly degenerates as they age. This is referred to as loss of Y (LOY).

Studies looking at the effects of this age-related decay of the Y chromosome have tentatively linked it with certain cancers. Some researchers believe that, in the future, LOY measurement may act as an early warning system for individuals who are particularly susceptible to some cancers.

Men are known to live shorter lives than women and are more likely to develop non-sex-specific cancers. Some scientists believe that the loss of the Y chromosome could help explain this gender difference.

Loss of Y and Alzheimer’s

Recently, Profs. Lars Forsberg and Jan Dumanski, from the Department of Immunology, Genetics, and Pathology at Uppsala University, Sweden, teamed up with scientists from the United Kingdom, France, the United States, and Canada.

Before turning to Alzheimer’s, Prof. Forsberg has previously worked on research investigating LOY and its effects on the progression and development of certain cancers.

“The idea for this research project came to me when I was writing our first paper on the relationship between LOY and the development of non-blood cancers. In thinking about the process known as immunosurveillance – the body’s ability to fight disease development throughout life – I found that it had been well studied in Alzheimer’s disease, and hence it occurred to me that LOY might be involved in this disease too.”

Prof. Lars Forsberg

The global team looked into the chromosomes of 3,200 men aged 37-96, with an average age of 73. Of this sample, around 17 percent of them displayed LOY in at least 10 percent of their red blood cells. LOY was most common in elderly men.

The team found that individuals who already had an Alzheimer’s diagnosis were more likely to have LOY. Also, those with LOY were more likely to develop the disease in the follow-up period.

Because blood cells play such an integral role in the immune system, the researchers wonder whether the LOY might lower the cell’s ability to function correctly in immune responses.

Research into LOY is still in its infancy, but the team hopes that further down the line, measuring LOY in individuals could act as a marker for diseases. Testing for LOY is relatively simple and, if carried out routinely, an increased LOY in a patient could be used as a signal to begin neurological testing or cancer screening, for instance.

Catching diseases sooner rather than later is always preferable, and tests like this have the potential to save, or at least extend, lives.

Learn more about modern research into Alzheimer’s.

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