Women’s unique immune systems and cells make them more susceptible to Alzheimer’s and auto-immune diseases than men.

Sexism, pollution and Alzheimer’s

Mel (Mary Ellen) Harte BY EHN 

Women are two to four times more likely to develop any of 100-plus chronic auto-immune diseases than men.

This could include Alzheimer's disease, which some researchers are starting to link to the immune system, the sixth leading medical cause of U.S. deaths. Women comprise two-thirds of diagnosed Alzheimer’s patients and often develop worse symptoms of memory failures and lower brain metabolism, than men. Why are they so susceptible?

While women’s unique biology plays a role, growing research also suggests chronic stress — often stemming from sexism — as well as tiny particles of environmental pollution may play a role in this disparity.

As we untangle the causes of Alzheimer’s and auto-immune diseases, we need to eliminate gender bias in health care, sexism, and the insidious contamination that may be driving disease in women.

Genetic susceptibility 

The presence of the gene APOE4 significantly increases the likelihood of developing Alzheimer's disease, especially for women.

Female auto-immune susceptibility also likely stems from their distinctive immune systems. Women generally have greater antibody responses than men. That difference could be evolutionary: pregnant women with higher levels of antibodies probably protected their children more from infections.

But there is a downside: female frequency of high antibody levels correlates with developing auto-immune diseases. As antibodies rise during pregnancy; more pregnancies increase susceptibility to auto-immune diseases. Menopause, a hormonally disruptive time for women, could also play a role. 

As estrogen levels decrease, so does the activity of the average female brain: up to 30%, wrote Lisa Mosconi, director of the Alzheimer’s Prevention program at Weill Cornell Medicine NewYork-Presbyterian Hospital, in her book “The XX Brain.” Women experiencing the greatest decreases are more likely to develop dementia. And although most women recover cognitively from menopause, antibody levels likely rise.

There’s also a newly discovered susceptibility lurking inside every female cell — one of the two X chromosomes deactivates itself to prevent overproduction of proteins used to regulate the immune and other systems. 

The deactivating chromosome produces a unique strand of nucleic acid, Xist RNA, which, with bound proteins, blankets and silences itself. Many of those bound proteins can alarm the immune system, causing it to produce autoantibodies against human proteins.

Why has it taken 60 years to understand how women’s biology increases their susceptibility to auto-immune diseases? One researcher suggested gender bias in medical research, noting that for several decades the standard research tool has been the male blood line, which, for example, doesn’t contain the Xist RNA mentioned above.

Sexism and chronic stress

Not all women develop auto-immune diseases. What triggers it in those that do?

Whenever alien protein structures or cell damage are detected, it triggers the immune system to release antibodies, creating inflammation. Evidence consistently links low-grade chronic brain inflammation to cognitive decline and Alzheimer’s disease, notes Mosconi in her book.

There are many causes of inflammation: lifestyle, genetics and aging, which results in cumulative damage and can cause the immune system to become mistakenly activated against the body’s own proteins. Behavioral stress can result in inflammation. 

Emotional stress can trigger release of the stress hormone cortisone, affecting the immune system. Exposure to cortisone from chronic stress increases susceptibility to problems including anxiety, depression and cognitive dysfunction, loss of memory or attention. Thus, chronic stress can make the brain more susceptible to infections that cause chronic inflammation.

Given that Alzheimer’s disease is basically a lethal, inflammatory cerebral process, the role played by female emotional stress stemming from abuse is clear: abusive partners, mostly men, can literally help drive many susceptible women into dementia. Abusers can do so unknowingly and incrementally over decades of contact with their victims, inducing chronic stress levels.

Even subliminal levels of sexism, Mosconi notes, can cause chronic stress, either through women's self expectations or expectations by others. Sexist colleagues, co-workers, family or social circle members can all contribute to the broad layer of chronic stress.

The role of nanoparticle pollution 

A rising but underexplored external source of inflammatory cell damage, especially for women, is nanoparticle pollution, stemming from fossil fuels, when burned or used in plastics. Nanoparticles, so tiny that they are difficult to detect, can penetrate the brain — and it seems the tiny particles are better able to do this with older people and those suffering from Alzheimer’s. 

U.S. women – with Black, Latinas, and indigenous women disproportionately represented – are nearly twice as likely to live in poverty than men and their low income communities tend to be more exposed to hazardous air pollution. As a result, these women are more likely to experience hazardous levels of nanoparticles from air pollution.

Fine particulate matter in air pollution comprises nanoparticles and much larger particles; various nanoparticles have been shown to cause respiratory and cardiovascular diseases. More recently, a study and anatomical analysis linked Alzheimer’s disease with exposure to fine particulate matter.

Auto-immune diseases have risen in the U.S. over the past three decades, while the production and use of plastics have exploded, as has human exposure to the breakdown products of plastics, microplastics and nanoplastics. 

Both products are capable of penetrating the brain and other organs. While it is currently impossible to directly link both things, it’s important to research the possible connections.

We already know that while most microplastics pass through our bodies, the remainder can activate the immune system and degrade into nanoplastics. 

Nanoplastics get absorbed directly through our lungs, skin, hearts, and digestive systems. They can penetrate cells, damaging internal cell structures, such as mitochondria.

Many toxicological studies have shown that microplastics also can damage and kill human cells, activating an immune response. Microplastics and nanoplastics are linked to increases in strokes and heart attacks and can also contain chemicals that mimic hormones, which can disrupt hormone levels and disrupt immune response. Finally, nascent animal studies indicate that nanoplastics can cause cellular brain damage, resulting in nerve disorders and behavioral changes.

Although personal plastic exposure from clothes to personal care is universal, women are far more internally exposed to nanoplastic sources than men via hygiene products like tampons and cosmetics. Conditioned by male-dominated marketing to use such products, women could be damaging their immune systems and their brains.

These new insights illustrate a far more complete picture: women exercise their immune system more often and intensely than men; they tend to over-produce a protein that activates pro-inflammatory genes; their X chromosomes create protein structures that can cause inflammatory autoimmune responses; they are more exposed to air pollution and plastics containing nanoparticles and women in a male-dominated society are experiencing unique, rising levels of stress that further heighten the risk of brain damage.

All of these factors comprise a far more significant risk of women developing Alzheimer’s than men.

As we increase research on the medical effects of plastic nano-pollution, we need to dramatically decrease fossil fuel and plastic use, which disproportionately harm women. Equally urgent is the need to abolish sexism.

Both changes are vital for the collective cognitive health of human populations and nations around the world.

Mel (Mary Ellen) Harte is a biologist who writes on population, climate change and environment at Climate Change Reports. She co-authored the first free online and still relevant climate change book (Cool the Earth, Save the Economy: Solving the Climate Crisis is Easy) in 2008; more recently she co-authored the paper “Underestimating the Challenges of Avoiding a Ghastly Future” and is currently working on a book about family planning.