Raquel Sanchez Varo
The Conversation*
Almost 120 years have passed since the German physician Alöis Alzheimer first described the neurodegenerative disease that today bears his name.
It all started as a result of the case with a demented patient named Auguste Deter.
The latest data on Alzheimer’s disease (AD) suggest that it was no coincidence that Auguste was a woman: we now know that around two-thirds of people affected are.
Specifically, a study carried out in 2017 already showed that in Europe 3.31% of men suffer from Alzheimer’s compared to 7.13% of European women – more than double. However, until relatively recently this difference had not been given all the importance it deserves.
Hormonal changes matter
The main risk factor for AD is age. Among the general population, it is more common for women to reach or exceed 85 years of age. Therefore, it had been assumed that they were more likely to suffer from it simply because they had a longer life expectancy.
However, we now know that this fact does not explain the clinical reality. As with many other diseases, the answer could be found in both biological differences due to sex and sociocultural differences (gender roles).
From a biological point of view, the hormonal changes typical of female aging have been in the spotlight of Alzheimer’s research for many years. This is where estrogens come into play, steroid hormones produced mainly by the ovaries, but also by the adrenal glands, adipose tissue and the brain.
In addition to its role in reproduction, estrogens are involved in other signaling pathways, some related to cognitive functions or neuroprotection.
Thus, they are molecules with antioxidant action, regulators of metabolism, immune response, neurogenesis and synaptic plasticity, which are critical for brain aging.
Without going any further, the hippocampus has 2 types of estrogen receptors. And it just so happens that this brain region, which is involved in memory and learning, is severely affected in Alzheimer’s patients from early stages.
Therefore, it is evident that the loss of estrogens (hypoestrogenism) due to menopause seems to have a lot to say. So much so that women who have had their ovaries removed under the age of 50 also have a higher risk of cognitive impairment and Alzheimer’s.
For this reason, for several decades, research has been carried out to find out if hormone replacement therapy (that is, providing estrogen in the form of medication at the beginning of or during the menopause) could have a neuroprotective function.
Work is also underway to optimize its application: the data suggests that there is a critical time window of administration in which this treatment could be most effective.
Specifically, it could be more useful if it is applied in the initial stages of menopause or in cases of surgical menopause. However, there are conflicting data, so more studies are needed to clarify this matter.
The microbiota affects brain health
On the other hand, in the last decade the importance of the populations of microorganisms that reside in the human body (microbiota) and their relationship with hormones and brain health has been discovered.
Specifically, a subgroup of these bacteria, called the strobolome, actively participates in the regulation of systemic estrogen levels. Therefore, probiotic therapies could also have indirect beneficial effects on the brain of menopausal women.
In fact, the microbiota also presents sexual dimorphism, being different between men and women, which is known as microgenderoma. These variations produce different degrees of susceptibility when suffering from certain pathologies.
The female brain could be more vulnerable
Stress is another known risk factor for Alzheimer’s, which seems to affect women more than men.
A recent study with animal models of this disease has shown that the brain of females is more vulnerable to the impact of stress than that of males, apparently due to a greater increase in the accumulation of beta-amyloid protein.
The incorporation of women into the world of work, together with housework, care and family reconciliation problems, mean that, in general, they experience more stress than men.
And this implies that social strategies aimed at eliminating gender differences could be very positive in reducing the risk of AD among women.
Towards 150 million patients
Alzheimer’s is one of the major pandemics of the 21st century. It is expected that there will be around 150 million patients with this neurodegenerative disease by 2050. In Spain today there are more than 800,000 people who suffer from this type of dementia, and it is estimated that this figure will rise above 1.2 million in the coming decades.
Unfortunately, at the moment there is no really effective cure or treatment against this neurodegenerative disease. Ignoring differences due to sex and gender may have contributed in some way to this delay.
Precisely for this reason, the Women’s Brain Project (WBP) emerged, an international non-profit organization based in Switzerland, made up of experts in different scientific disciplines.
WBP was born from this need to analyze what are the differences that depend on sex and gender in mental health and illnesses, in order to apply this knowledge for the sake of precision medicine.
What is becoming increasingly clear is that sex is a significant variable that, unfortunately, has not yet been given the importance it deserves, despite dividing the world population into two physiologically well-differentiated subgroups. This point could explain, at least in part, the failure to transfer preclinical data to clinical trials, not only for Alzheimer’s, but also for other diseases.
*Raquel Sánchez Varo is assistant professor of the Histology Area of the Faculty of Medicine of the University of Malaga (Spain).
*This article was published on The Conversation and reproduced here under the Creative Commons license. Beam click here to read the original version.
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* Alzheimer’s: How to reduce the risks
* The dangerous relationship between blood pressure and Alzheimer’s
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