Scientists find sex gene risk for Alzheimer’s in certain females


New York: A gene found on the X chromosome harbours the first sex-specific genetic variant linked to a greater susceptibility to Alzheimer’s, according to a new study.

Researchers at the Mayo Clinic in Jacksonville, Florida and Rochester, Minnesota showed that women who inherited the same variant of the gene, known as PCDH11X, from both parents were far more likely to develop the disease.

Among Alzheimer’s patients evaluated for the study, “the odds a women had two copies of the PCDH11X variant as opposed to no copies was nearly twice as high as for the control group,” the lead researcher, Steven Younkin, told AFP by email.

Both men and women with only a single copy were also slightly more likely to have Alzheimer’s. But only women have two X chromosomes, making them uniquely vulnerable to the impact of the double variant.

Men have one Y chromosome, and one X chromosome.

Alzheimer’s is a degenerative disorder of the brain characterised by forgetfulness, agitation and dementia. There is no known cure.

While many gene variants, or alleles, have been implicated in the onset of the disease, only one other — APOE 4 — has been shown to be a higher risk factor.

The findings, published in the journal Nature Genetics, do not necessarily mean that women as a whole are more prone to getting Alzheimer’s.

“There may be male-specific risk factors — genetic or environmental — that balance the increased risk in women from PCDH11X variant,” Younkin explained.

The researchers discovered the wayward string of DNA by scanning the entire genome of 844 patients and 1,255 healthy persons, looking for telltale markers that might point to a genetic culprit.

After identifying PCDH11X, they confirmed the “highly significant association” by repeating the gene tests on an even larger group of 1,547 patients, and a slightly smaller number of controls.

Follow up studies will investigate the exact mechanism by which the variant affects the nervous system in order to help diagnose the disease early on and develop suitable drugs, Younkin said.

Alzheimer’s is caused by a massive loss of cells in several regions of the brain, driven by a buildup of plaques of amyloid protein. The disease occurs most frequently in old age.

An estimated 37 million people worldwide live with dementia, with Alzheimer’s disease causing the majority of cases, according to the World Health Organisation (WHO).

With the ageing of populations, this figure is projected to increase rapidly over the next 20 years.