Research suggests why women may be at increased risk of dementia

Dr Zoe says walking can reduce risk of dementia

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Every person born as a biological female has a pair of X chromosomes, thread-like structures inside our cells. During the early development of these chromosomes when someone is in an embryonic state one of these two will be inactivated.

As a result, all people born biologically female have one X chromosome which is transcriptionally active; this stops the overexpression of certain genes, but not all of them.

The new research suggests one of these genes, known as USP11, escapes and increases the risk of Alzheimer’s disease in women through its activation and its contribution to the accumulation of tau protein.

The accumulation of tau protein is thought to be the leading cause behind the development of Alzheimer’s disease. Patients with the condition have tangles of this protein around their nerve cells which disruptions their ability to communicate with another.

Writing in the journal, the authors wrote that USP11 “augments pathological tau aggregation via tau deubiquitination initiated at lysine-281. USP11 escapes complete X-inactivation, and female mice and people both exhibit higher USP11 levels than males”.

They added: “Genetic elimination of usp11 in a tauopathy mouse model preferentially protects females from acetylated tau accumulation, tau pathology, and cognitive impairment. USP11 levels also strongly associate positively with tau pathology in females but not males.

“Thus, inhibiting USP11-mediated tau deubiquitination may provide an effective therapeutic opportunity to protect women from increased vulnerability to AD and other tauopathies.”

They concluded: “Overall, our unbiased identification of USP11 as a DUB driving strong female-biased effects on tauopathy in humans and mice underpins a new mechanistic basis for greater vulnerability to tauopathy in women from a preclinical stage.”

Furthermore, the authors added: “In addition to presenting novel insights for preventing human tauopathies in women, this study also sets a framework for identifying other X-linked factors that could confer increased susceptibility to tauopathy in women.”

What this means is that their research could improve scientists’ understanding of why women are more at risk of Alzheimer’s than men and open a new avenue of research.

Furthermore, should the results of this research be reflected in other studies on the subject, it could potentially lead to new treatments which help to reduce the risk of dementia, a disease which takes the lives of 67,000 people in the UK every year.

However, this is only what could happen rather than what is happening right now; dementia remains a fierce foe in the scientific and health community.

What have experts said about the study?

Speaking to Medical News Today, Professor Julie Williams of Cardiff University said: “I would not go far as saying it’s causing the sex difference, but it may be contributing, but there’s a bit more work that needs to be done to really stand that up. But it is a very interesting and novel finding.”

Professor Williams added the findings “were of great interest to the field” and highlighted the numerous studies which had come before this research set. However, she acknowledged that the USP11 gene had not yet been looked at.

Meanwhile, Professor Bart De Strooper added: “[I]t should be noticed that evidence is largely gathered in a preclinical setting, in models of the disease such as cell cultures and mouse models, but that the experiments are sound and indeed support the overall conclusions of the paper.

“I would say that this work deserves further follow-up by drug developers to see whether the X-linked ubiquitin peptidase can be targeted in the context of Alzheimer’s and frontotemporal disease.”

What are the main symptoms of Alzheimer’s disease?

Alzheimer’s disease is the most common form of dementia. Early symptoms include:
• Forgetting about recent conversations or events
• Misplacing items
• Forgetting the names of places and objects
• Have trouble thinking of the right word
• Ask questions repetitively
• Show poor judgement and find it harder to make decisions
• Becoming less flexible and more hesitant to try new things.

As the disease develops, these symptoms can worsen. Eventually, Alzheimer’s disease, like all forms of dementia, causes the death of the patient.

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