Why women face a higher risk of Alzheimer’s

Summary: women have almost twice as probabilities that men to develop Alzheimer’s disease, a disparity that cannot be completely explained by longevity alone. Researchers are exploring biological differences, focusing on genes linked to X chromosomes and hormonal changes such as menopause.

Decreases in estrogen during menopause can allow the brain to be more vulnerable to tango tau tau that boost cognitive deterioration. Understanding these sex -based differences could lead to better and more personalized treatments for Alzheimer’s and related conditions.

Key facts:

The two X chromosomes of women and imperfect silencing can influence Alzheimer’s risk through immune and brain -related genes. Drops related to estrogen menopause seem to increase vulnerability to tauwal tangles in brain tangles.

Source: Harvard

A careless piece of Alzheimer’s puzzle has increased scientific attention: why women have twice as probabilities that men to develop the disease.

One could be tempted to explain disparity as a natural consequence of women who live more. But those who study the disease say that would not explain such a large difference, and are not precisely sure of what I would.

While many factors may be at stake, researchers are concentrating in two where biological differences between women and men are clear: chromosomes and menopause.

Women have two X chromosomes, and men have an X E Y. The differences between the genes that are maintained in the X and Y chromosomes, according to the researchers, can give women a greater possibility of developing Alzheimer’s.

Menopause, when the production of estrogen and progesterone hormones decreases, is another clear difference between the sexes. These hormones are widely known for their roles in the reproductive system, but estrogen also acts on the brain, researchers say.

Whatever is at stake, it is probably part of the deepest neurological processes, researchers say, pointing to similar differences related to sex in other conditions. Multiple sclerosis and migraine, for example, are more common in women.

Parkinson’s disease, brain tumors and epilepsy, on the contrary, are more common in men. In some cases, such as migraine in women and Parkinson in men, the increase in gravity accompanies a greater incidence.

“Epidemiologically, we see that for almost all neurological diseases, there are differences in how many biological women and men are affected,” said Anna Bonkhoff, resident and researcher in neurology at Harvard Medicine School and General Mass Brigham.

“There is a trend, for example, in EM and migraine so that more females are affected, while it is the opposite for brain tumors and Parkinson’s. Only according to these numbers, you have the feeling that something needs to undereate these differences in terms of biology.”

Basic construction blocks are genes, which in humans are arranged in 46 chromosomes, organized in 23 pairs. One of those couples, XX in women and Xy in men, contains the genes that define the characteristics based on sex, differences that are key areas of exploration.

The x and y chromosomes differ significantly, Bonkhoff said.

The X chromosome is rich in genes, while the chromosome and has lost a significant number during the millennia. However, having two X chromosomes does not mean that women have a double dose of proteins and other genetic products produced by those genes, because one of the X chromosomes is silenced.

However, that silencing is imperfect, said Bonkhoff, leaving some genes on the X -silenced active chromosome. Studies have shown that genes on the X chromosome are related to the immune system, brain function and Alzheimer’s disease.

“We know that biological men and women differ in the number of X chromosomes,” said Bonkhoff, lead author of a recent review article in the journal Science Advances that examined the differences related to sex in the disease and stroke of Alzheimer’s stroke.

“Many genes for the immune system and the structure of the regulatory brain are found in the X chromosome, so the doses differ to certain degrees between men and women. That seems to have an effect.”

Another key difference between men and women is related to their hormones. All humans have three sex hormones: estrogen, progesterone and testosterone. In women, estrogen and progesterone dominate, while in men dominates testosterone.

When one looks at the changes between men and women with respect to hormones and aging, menopause is a significant link in the course of their life.

“Menopause is part of the puzzle, probably one of the greatest,” said Bonkhoff. “I do not say that it is the only one: aging is relevant by itself, and there are many interesting research looking at what aging does to the immune system that seems to have implications for cognitive changes.”

Women generally go through menopause from the mid -40 to the mid -50s. During that time, their ovaries stop producing estrogens and progesterone, resulting in the characteristic symptoms of menopause, such as stifling, emotional changes, ceases menstruation, difficulty sleeping, among others.

In March, Rachel Buckley, associate professor of neurology at Harvard’s Faculty of Medicine, and her colleagues followed that hormonal thread in a study that examined the impact of hormonal replacement therapy and the accumulation of the Tau protein in the brain, a key characteristic of Alzheimer’s disease.

Buckley, who is also a neurology researcher at the Massachusetts General Hospital, discovered that women who received hormonal replacement therapy later in life, after 70 years, had significantly higher levels of TAU accumulation and suffered a greater cognitive decrease.

The result, he said, supports the “time” approach to hormonal therapy, which argues that hormonal replacement therapy can be used safely to relieve the symptoms of menopause, but should not continue in old age.

The synchronization theory arose in response to a study conducted by the Women’s Health Initiative funded by the Federal Government in the early 2000s, which showed an association between women who take hormonal replacement therapy and the increase in cognitive deterioration. That was contrary to the expectations of previous studies that indicated that estrogen had protective effects on cognition.

Subsequent studies, however, showed that hormonal therapy seemed to be protective in younger women, but associated with the decrease in cognition in women 65 years and older.

Buckley’s research took that job one more step, linking it with physiological changes in the brain. Alzheimer’s disease implies the accumulation of beta amyloid in characteristic plaques in the brain, considered an important distinctive seal of the condition. These plates stimulate the development of tangles of a protein called Tau, which then causes harmful inflammation.

Buckley’s research showed that hormonal therapy among older women was associated with an increase in Tau and with cognitive decline. It was not associated with an increase in beta amyloid, which today is a common therapeutic objective.

The investigation, published in the journal Science Advances in March and financed in part by the National Aging Institute, allowed Buckley, Gillian Coughlan, first author and instructor in Neurology, and his colleagues to highlight the role of the hormonal replacement in the accumulation of Tau’s tangles in older women.

But Buckley said the study also highlights significant areas where the work to be done is.

The database used for the study did not have information about variables that can be important, such as the reproductive history of a woman, the information about when replacement therapy and the duration of the use of hormonal therapy began.

Understanding the importance of these missing data, Buckley said, is a step forward despite the fact that the fact that it limits the conclusions that can be made in your study.

To remedy that, Buckley is planning her own study that will collect what she thinks are all the relevant data, including reproductive history, and the details of the use of hormonal therapy.

“We work with many secondary data that already exists, and that is great, but there are limitations to what we can do with it,” Buckley said.

“We are trying to see if we can configure a new study design where we can really see the moment of menopause, which is changing in the blood, which is changing in the brain, which is changing in cognition and how that could be associated with the risk of later life.”

Suspending how biological sex affects Alzheimer’s risk, said Bonkhoff and Buckley, can help us understand Alzheimer’s in general. That understanding, they said, has the potential to lead to new routes of treatment and prevention of a disease that, despite the decades of research and encouraging recent progress, is still known little.

“It is an important objective in medicine to understand and then innovate how we can prevent or treat,” said Bonkhoff.

“If we can find ways to incorporate sex difference to optimize treatment for individuals, both men and women, that is the general objective.”

On this Research News of Alzheimer’s disease

Author: Alvin Powell
Source: Harvard
Contact: Alvin Powell – Harvard
Image: The image is accredited to Neuroscience News

Original research: open access.
“Sex differences in neurological diseases associated with age, a roadmap for reliable and high performance research” by Anna Bonkhoff et al. Advancement of science

Abstract

Sex differences in neurological diseases associated with age: a roadmap for reliable and high performance research

Once taken into consideration, sex differences in neurological diseases arise in abundance: (i) the seriousness of the accident

While these differences receive increasing attention in isolation, they are probably linked to similar processes in the brain.

Therefore, this review aims to present an overview of the influences of sex chromosomes, hormones and aging of male and female brains in health and disease, with a particular approach to EA and stroke.

The approach here in the advances in several fields promises to boost future research and lead to an enriched understanding of the brain and more effective personalized neurological care for all.