Women are More Prone to Alzheimer’s Disease and Stress May Be the Culprit

Summary: Stress may be a factor in why women are twice as likely as men to be diagnosed with Alzheimer’s disease. Amyloid beta rose sharply in the brains of female mice but not males during stressful situations. A molecular pathway that is active in brain cells from female mice but not males accounted for the divergent responses to stress. Reducing stress may be more beneficial for women than men, in terms of lowering the risk of Alzheimer’s disease.

Key Facts:

  1. Stress releases a hormone called corticotropin releasing factor, which causes the rise of the Alzheimer’s protein amyloid beta in the brain of female mice but not male mice.
  2. Stress is not the only factor contributing to the sex difference in Alzheimer’s disease, but it is driving one aspect of this difference.
  3. Other differences between men and women, such as hormones, lifestyle, and other diseases they have, also contribute to the sex difference in Alzheimer’s disease.

Source: WUSTL

Women are about twice as likely as men to be diagnosed with Alzheimer’s disease. Some of that is age; in the U.S., women outlive men by five to six years, and advanced age is the strongest risk factor for Alzheimer’s.

But there’s more to it than that, so Alzheimer’s researchers continue to look for other reasons why women have an elevated risk of the deadly neurodegenerative disease.

Stress may be one such reason. A study by researchers at Washington University School of Medicine in St. Louis shows that the effect stress has on the brain differs by sex, at least in mice.

In stressful situations, levels of the Alzheimer’s protein amyloid beta rises sharply in the brains of females but not males. In addition, the researchers identified a molecular pathway that is active in brain cells from female mice but not male mice, and showed that it accounts for the divergent responses to stress.

The findings, published May 2 in Brain, add to a growing collection of evidence that sex matters in health and disease.

From cancer to heart disease to arthritis, scientists have found differences between males and females that could potentially affect how men and women respond to efforts to prevent or treat chronic diseases.

“How women respond to stress versus how men respond to stress is an important area of research that has implications for not just Alzheimer’s disease but other conditions, too,” said co-corresponding author Carla M. Yuede, PhD, an associate professor of psychiatry.

“In recent years, the National Institutes of Health (NIH) has prioritized understanding sex differences in medicine. Stress is one area in which you can clearly see a difference between males and females. This study shows that reducing stress may be more beneficial for women than men, in terms of lowering the risk of Alzheimer’s disease.”

Stress falls into the category of socioeconomic risk factors, along with factors such as depression and social isolation, that together account for an estimated 8% of the risk of developing Alzheimer’s. That risk calculation, however, doesn’t take gender into account.

Women consistently report higher levels of stress than men, and stress affects women’s bodies differently than men’s in many ways, such as cardiovascular health, immune responses and other issues.

This shows a stressed woman
From cancer to heart disease to arthritis, scientists have found differences between males and females that could potentially affect how men and women respond to efforts to prevent or treat chronic diseases. Credit: Neuroscience News

Corresponding author John Cirrito, PhD, an associate professor of neurology; Yuede; and first author Hannah Edwards, a graduate student in Cirrito’s lab, reasoned that stress also may affect women’s brains differently than men’s, and these differences may help explain the sex imbalance in Alzheimer’s disease.

To find out, they measured levels of amyloid beta — a key Alzheimer’s protein — in the brains of mice every hour for 22 hours, beginning eight hours before the mice experienced stress. The experience was equally stressful for male and female mice, as measured by the levels of stress hormones in their blood. But the responses in their brains were not the same.

In female mice, amyloid beta levels rose significantly within the first two hours and stayed elevated through the end of the monitoring period. In male mice, brain amyloid levels did not change overall, although about 20% of them did show a delayed and weak rise in amyloid levels.

Further experiments revealed that the difference comes down to a cellular stress response pathway in brain cells. Stress causes the release of a hormone known as corticotropin releasing factor.

Neurons from female rodents take up the stress hormone, triggering a cascade of events that results in increasing levels of amyloid beta in the brain. In contrast, neurons from male rodents lack the ability to take up the stress hormone. It is not known whether there are similar sex differences in how human neurons take up stress hormones.

“There’s a fundamental biological difference between males and females in how they respond to stress at the cellular level, in both mice and people,” Cirrito said.

“We don’t think that stress is the sole factor driving the sex difference in Alzheimer’s disease. There are many other differences between men and women — in hormones, lifestyle, other diseases they have — that undoubtedly contribute in some way. But that stress is driving one aspect of this sex difference I think is very likely.”

About this Alzheimer’s disease and stress research news

Author: Judy Martin Finch
Source: WUSTL
Contact: Judy Martin Finch – WUSTL
Image: The image is credited to Neuroscience News

Original Research: Open access.
Sex-dependent effects of acute stress on amyloid-β in male and female mice” by Carla M. Yuede et al. Brain


Sex-dependent effects of acute stress on amyloid-β in male and female mice

The risk of developing Alzheimer’s disease is mediated by a combination of genetics and environmental factors, such as stress, sleep abnormalities and traumatic brain injury. Women are at a higher risk of developing Alzheimer’s disease than men, even when controlling for differences in lifespan.

Women are also more likely to report high levels of stress than men. Sex differences in response to stress may play a role in the increased risk of Alzheimer’s disease in women.

In this study, we use in vivo microdialysis to measure levels of Aβ in response to acute stress in male and female mice. We show that Aβ levels are altered differently between female and male mice (APP/PS1 and wild-type) in response to stress, with females showing significantly increased levels of Aβ while most males do not show a significant change.

This response is mediated through β-arrestin involvement in Corticotrophin Releasing Factor receptor signalling pathway differences in male and female mice as male mice lacking β-arrestin show increase in Aβ in response to stress similar to females.

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  1. Donna Miller,

    Here is a video from the website of an organization called, UsAgainstAlzheimers.org .
    The video is apparently an interview with Dr. Mary Newport, MD.
    (I’ve heard from and read of her many times in past years, though haven’t listened to all this video.)

    To find help, 2 of the “functional medicine” practicing MDs in the USA who I would recommend to you
    for their books, websites, newsletters, PBS info packages (and PBS may still have some from other medical doctors who practice “functional medicine” and focus on the brain), or subscriptions, including to online communities, are

    Dr. Dale E. Bredesen, MD, a neuroscientist who has published research evidence supporting his effective protocol against Alzheimer’s, and you can benefit now even though your symptoms have begun and are considerable. He can be found online. (I think also at Apollo.)

    Dr. Daniel G. Amen, MD, also a neuroscientist. He has great books, and, through PBS offers good information packages. Both kinds of resources educate people on what they can do to slow and reverse or prevent Alzheimer’s.
    He has a website.

    Very best of luck to you, Donna Miller. DON’T give up! Start where you are right now, with whatever resources you have, even if they are very small. Start today. Now is the best time to start. Take steps everyday to identify things that people can do to strengthen their brain health. There are lots of do-able things. (Many cost nothing or little.)

    And some swaps or measures can even begin to produce positive change in 1-3 months.

    Here are just a few, higher impact measures — to get your brain strengthening started until you have checked resources like those of the 2 medical doctors above.

    ie. Reducing insulin resistance (increasing insulin sensitivity), and reducing and regulating blood sugar. (ie. Get an A1C blood test and take measures to lower your number every 3 months when you take your next A1C blood test.)

    Go to bed and sleep EARLY and consistently, in pitch dark, silence, breathing only through your nose (consider taping lips if necessary to train your brain), NEVER on your back, ideally on your Right side; if not, Left side is still better than on back. Sleep 8-9 hours. Not more. No day naps longer than ~15 minutes. No blue light in the evenings. No food or calories 3-4 hours before sleep time. 12 to eventually 16 hours of fasting every night.

    The brain shrinks, irrigates, and tries to clean out metabolic wastes while you sleep, especially in those hours BEFORE around midnight.

    Get bright early morning light everyday. (Or use a device that provides such.)
    Among other benefits, this will help your hormones and you be consistent about your early sleep time.

    Remove ALL added sugars from your diet.
    Before meals containing carbohydrates or protein, take a blood sugar mitigating herbal supplement.

    Remove all industrial and bad fats from your diet. (Including NO canola, soybean, “vegetable,” or seed oils.)

    Instead, use unheated, cold pressed olive oil, or (cold or on low-heat) virgin coconut oil.
    #1 Though: If you smoke, you need to quit. It’s out of a person’s system in about 3 days.
    – A notebook for personal strategies and thoughts is helpful.
    – Alan Carr books are helpful.
    – “The Shift” device breathing practices are helpful. (I have no vested interests whatsoever.)

    Eat lots of vegetables everyday. Start even with your first meal of the day.
    Eat green leafy vegetables everyday.

    Eat 1/2 Cup of berries everyday that you can afford to.

    Incorporate some gratitude practices into your day.

    Incorporate some deep breathing practices into every morning and your day, including with exhalations of 12 seconds. (Scientific reasearch.)

    If you don’t have one yet, create a relationship with God.

    Consider joining groups or an organization —

    either for meaningful friendships,
    or for sharing activities that you can learn or enjoy,
    or for sharing common interests,
    or where you can create or build,
    or where you can move, walk, or otherwise exercise with other people.

    Do everything you can to prevent depression, overwhelm, and anxiety.
    Physiologically, socially, spiritually, emotionally, psychologically.

    Spend time outdoors at least 2 times a day.

    What’s strengthens the heart or other muscles strengthens brain health.
    If you have a mini trampoline, exercise bike, other cardio equipment, put them to work everyday.

    Get up and move for at least 5 minutes of every waking hour.

    Everyday, hold positions that strengthen muscles.
    For instance, proper squats, planks, wall push-ups, balancing on one leg, certain yoga positions.

    Consider yoga.

    Consider dancing.

    Consider creating a daily ritual of relaxing while focusing on nothing but listening to classical music for a period of time.

    Filter your drinking water.
    Eat cilantro.
    Obtain a protocol for removing heavy metals from your body (ie.) by consulting with either an MD who practices “functional medicine” or with a Naturopathic Doctor / ND.

    Et cetera. There are many more effective measures that you can take to strengthen your brain health.

    Your brain health is worth strengthening. You and your spirit are worth renewing.

    All the very best to you, Donna Miller (of May 4, 2023 at 7:31 am).

  2. I do NOT believe it.
    Basically women are more likely to keep their spouse at home as long as possible.
    Men are more likely to dump their wives at a care home when they get confused

  3. OK doesn’t take 8 yrs of Ed to figure out , women have more stress.
    My Male Doc looks at me and said, well maybe next time you come
    in we can discuss it………….so nobody willing to discuss it. Memory loss
    I keep fall down, my hair has fallen out, what day is tomorrow?
    I’m done. hope I find my way home, my car, oh where did I park?
    Oh its lunch time! did I feed the dog? I did take a shower this week.
    I can’t remember the code to the lock box, so I just don’t lock the door.
    Who will help me, am 77 and …………….

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