Gene Variant Confers Higher Alzheimer’s Risk For Women

Brett Smith for – Your Universe Online

New research from scientists at Stanford University has revealed a genetic variant that raises the risk of developing Alzheimer’s disease in women, but not in men.

After analyzing information on numerous older individuals who were followed over time, the scientists recognized a genetic variant called ApoE4 that conveyed the sex-specific elevated risk level, according to their report in the Annals of Neurology.

While more women suffer from Alzheimer’s than men, women also tend to live longer increasing their odds of developing the cognitive disorder. However, the study researchers found the risk from the genetic variant remained even after considering age.

“Even after correcting for age, women appear to be at greater risk,” said Dr. Michael Greicius, study author and assistant professor of neurology at Stanford.

In the study, researchers considered records that had been stored in two large, openly available databases. In one repository, the scientists reviewed clinical assessments of 5,000 people whose cognitive test outcome was normal at the start and 2,200 people who had originally showed indications of mild cognitive impairment.

Within both groups, being an ApoE4 carrier showed higher probability of Alzheimer’s disease. Additionally, the team also saw that for those who began with normal cognitive function, the greater risk was only minimal for men, while women who had the ApoE4 variant had near double the odds of moving on to mild cognitive impairment or Alzheimer’s disease as people who didn’t.

“Our study showed that, among healthy older controls, having one copy of the ApoE4 variant confers a substantial Alzheimer’s disease risk in women, but not in men,” Greicius said.

From the second database, researchers examined imaging information and measurements of a number of biomarkers from spinal fluid that signal mild cognitive impairment and ultimately Alzheimer’s disease. Evaluation of 1,000 patients’ files from this collection not only validated ApoE4’s sex-specific effect, but it also produced evidence that may assist investigators in exploring, and potentially explaining, the molecular components connecting ApoE4 to Alzheimer’s disease, Greicius said.

The ApoE gene codes for a protein vital for moving fatty substances all over the body. This is especially critical in the neurological system, as brain function relies on quick rearrangement of these kinds of fatty substances along and among nerve cell membranes. The ApoE gene can be seen in three varieties – ApoE2, ApoE3 and ApoE4 – which are inherited based on variants in the gene’s sequence. This means that the Apo protein also comes in three versions, whose constructions and performances differ.

Most people carry two versions of the ApoE3 gene variant – one from each parent. However, approximately 20 percent have at least one copy of the risk-elevating ApoE4 gene, and a small proportion has two ApoE4 copies. Several previous reports have validated that ApoE4 is a high-risk factor for Alzheimer’s disease, with one copy of ApoE4 doubling or quadrupling that risk. Having two copies has been found to boost the risk of Alzheimer’s by 10 times.

Greicius said the results of the study means clinicians need to take different approaches to Alzheimer’s patients based on their sex.

“These days, a lot of people are getting genotyped either in the clinic or commercially,” he said. “People come to me and say, ‘I have an ApoE4 gene, what should I do?’ If that person is a man, I would tell him that his risk is not increased much if at all. If it’s a woman, my advice will be different.”

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