Alzheimer’s disease is still a mysterious disease – and the main trigger for dementia. According to current estimates by Alzheimer’s Disease International (ADI), the gradual decline in cognitive, emotional and social skills affects around 47 million people worldwide and is now the seventh leading cause of death worldwide. According to the German Alzheimer Society, around 1.6 million people live with dementia in Germany alone – and most of them are Alzheimer’s patients.
Almost 120 years after its discovery, it is still not really clear what causes the disease. An equally big mystery is why about two thirds of dementia patients are women – and why they usually get even more seriously ill than male patients. Many factors are suspected of making women particularly susceptible to the development of brain-damaging protein plaques: women live longer than men and the risk increases with age. There is evidence that the number of children and the length of a woman’s reproductive life has an impact on the risk of dementia – in connection with estrogen levels. Earlier this year, researchers at Emory University School of Medicine published in Nature that another hormone could trigger Alzheimer’s in women: the follicle-stimulating hormone FSH, which the pituitary gland secretes in excess at the onset of menopause.
Trigger still unclear
And parallel to all these theories, the genes are still suspect. The apolipoprotein E (ApoE) genotype is the largest known genetic risk factor for Alzheimer’s disease. The ApoE protein transports cholesterol, among other things, to neurons that need it for myelin production and thus for signal exchange.
Although ApoE-e4 is a risk factor for Alzheimer’s, it does not necessarily trigger the disease: Many healthy older people are ApoE-e4 positive and a large proportion of Alzheimer’s patients are definitely ApoE-e4 negative. About a quarter of people with a European genetic background carry this gene variant. Among Alzheimer’s patients it is 60 percent. Researchers from the University of Chicago and the Boston University School of Medicine have concluded that there must be other genes that predispose people to Alzheimer’s. And they found what they were looking for: The MGMT gene increases the risk of Alzheimer’s in women.
Investigations in an isolated gene pool
They found this connection through two genome-wide association studies. In this type of study, the researchers examine two groups: the comparison group shows no signs of the disease – or any other trait – while the second group shows the traits for which matching genes are being sought. DNA samples are taken from both groups and examined for differences.
In the first of their two studies, the researchers examined dementia in a large Hutterite family. This is a United States and Canada based denomination originally from Europe. She named herself after the Baptist Jakob Hutter. The Hutterites live in closed colonies and have developed an isolated, relatively small gene pool over the centuries that the communities have existed (the first colony was established in 1528). In the study, the people with Alzheimer’s disease were exclusively women.
Specific risk factor for women
In the second study, the Chicago scientists investigated a link between Alzheimer’s and breast cancer. They examined the genetic data of a group of 10,340 women who were ApoE-e4 negative – meaning they didn’t have the most well-known genetic susceptibility to Alzheimer’s in their genes. In both sets of data, they found a direct and strong link between the MGMT gene and the development of Alzheimer’s.
“This is one of the few and perhaps the strongest association of a genetic risk factor for Alzheimer’s that is specific to women,” said Lindsay Farrer, PhD, chief of biomedical genetics at BUSM and senior author of the study. “This result is particularly robust because it was discovered independently in two different populations using different approaches.”
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