The female brain ages more slowly than the male brain. Why isn’t he protected from Alzheimer’s?

As we age, a healthy male brain loses more volume and in more brain areas than a healthy female brain. This is supported by a study published in Proceedings of the National Academy of SciencesIn short, structural changes in the brain linked to aging do not seem to explain why women are almost twice as likely to be diagnosed with Alzheimer’s disease as men.

Since rapid brain aging is one of the most important risk factors for Alzheimer’s, one might have expected a more pronounced decline of the female brain in the areas most affected by this form of dementia. But the new work, conducted by a group of neuroscientists at the University of Oslo (Norway) shows that the most significant age-related losses of gray matter are found in the male brain.

Scientists observed the evolution over time of the brain structure of more than 4,700 healthy people, who did not suffer from Alzheimer’s or even mild cognitive decline, and who participated as control subjects in 14 large health studies. In all, 12,500 functional magnetic resonance imaging (MRI) brain scans were analyzed – at least two per person, performed on average 3 years apart.

The images made it possible to understand, for example, how the thickness of the gray matter (the tissue made up of the bodies of neurons) had changed over time, and whether the brain areas most affected by Alzheimer’s, such as the hippocampus, an essential structure for memory, had shrunk.

In general, the brain tests of men indicated a more substantial and more widespread reduction in volume than those of women. As is known, men also have a lower life expectancy than women.

The research – not without limitations, such as having considered people with high levels of education as a protective factor on brain aging and not necessarily extended to the majority of the population – seems to suggest that the greater female predisposition to Alzheimer’s is not to be found in the speed at which the brain ages, but in other factors that make them more susceptible to this dementia.

The sex chromosome A University of California – Los Angeles Health Sciences study conducted on mice and published in Science Translational Medicineidentified a gene on the X chromosome that promotes inflammation in the brain’s immune cells, which together are called microglia.

Just because they have two X chromosomes, female mice are more susceptible to this inflammatory process, and they also show greater benefits when the gene (called Kdm6a) and its associated protein are deactivated. Californian scientists tried to pharmacologically silence the protein encoded by the gene using metformin, an anti-diabetic that appears to have anti-aging properties.

The idea is that the gene and its inflammatory activity are advantageous for fighting infections in childbearing age, and that they are kept in check by estrogen, hormones with anti-inflammatory and neuroprotective properties. With menopause and the decline in estrogen, the inflammatory effects of the gene become neurologically harmful.