Among men and women, Alzheimer’s prefers women. Suffice it to say that in Italy out of 600,000 people affected by the disease, two thirds belong to the female gender, and that in the United States out of 5.8 million cases, women are 6 out of 10 patients. greater prevalence of the disease among women is longevity – females live on average 5.4 years longer than males – and the drop in estrogen levels associated with menopause. To these today is added a gene whose variants would explain in a different way why the risk of incidence of the disease in women is so high. It is MGMT, a gene that contains the instructions for the production of a protein capable of repairing DNA damage, and would be the basis of one of the few, and perhaps strongest, associations between a genetic risk factor and the Alzheimer’s never detected in women, assure the authors of the discovery. The study was conducted by a group of researchers from the University of Chicago and Boston University School of Medicine (BUSM) and the results were published in Alzheimer Disease & Dementia.
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By analyzing the gene expression of MGMT, i.e. what happens when a gene is turned on or off, the researchers noted two important elements: this process is linked to the development of beta-amyloid and tau, the proteins that accumulate causing the death of nerve cells. A correlation observed mainly in women. But not only: this same association is more pronounced in women not affected by APOEε4, the genetic variant considered to date the main risk factor for the development of the disease in men and women over 65. 60% of people of European origin with Alzheimer’s he is a carrier of this variant, but many women with APOEε4 are not affected by the disease and those who do not have this allele can instead develop it, to underline the non-deterministic character of the association.
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To achieve this, the scientists conducted two different genome-wide association studies (so-called genome-wide association studies, GWAS) for Alzheimer’s, i.e. two investigations into the genes of individuals belonging to different populations, capable of identify genomic variants statistically associated with the risk of developing dementia. The samples were very different: one of just thirty people (22 women), from a large extended family of Hutterites in which all those with Alzheimer’s were women. The other sample was that of over 10,000 women with APOEε4 levels equal to zero. In one case the approach was to focus on the genetic heritage of a generally rather isolated population, the other was inspired by the existence of a possible link between Alzheimer’s and breast cancer. In both sets, the researchers found a very strong association between MGMT gene variants and Alzheimer’s in women. More than the presence of the variants per se, the authors underline, it would be their expression (epigenetically regulated) that is correlated to the typical markers of the disease.
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There is still a long way to go
However, even if the study results are consistent in two very distinct cohorts, further follow-up analyzes are still needed in other GWAS datasets, the experts conclude. In order to develop new potential therapeutic approaches, it is necessary to better understand the role of the gene associated with Alzheimer’s in both women and men, and the reasons why only women would increase the risk of developing the disease, especially in those without APOEε4. .