Why Are Men More Prone to Parkinson's Disease? — Gender Differences Found in the Brain's "Supporting Cells"

Tremors in the limbs, slowness of movement, muscle stiffness, and difficulty maintaining posture. Parkinson's disease is a progressive neurological disorder that manifests various symptoms due to the gradual loss of cells that produce the neurotransmitter dopamine, which regulates movement.

However, the impact of the disease is not limited to motor functions. Non-motor symptoms, such as decreased sense of smell, constipation, sleep disorders, pain, mood depression, and cognitive changes, which are not easily visible, also significantly affect the quality of life.

This disease has long been known to have a clear gender difference. Although the numbers vary depending on the region and research methods, studies mainly from Europe and the United States report that the incidence and prevalence in men are about 1.5 to 2 times higher than in women.

However, while the fact that "there are more men" is known, the reason why there are more has not been sufficiently explained.

Possible explanations include the higher likelihood of men working in occupations such as agriculture, metalworking, and petrochemicals, where they are more exposed to pesticides and chemicals; the possibility that the female hormone estrogen provides some protection to nerve cells; differences in genetic function, immune responses, lifestyle habits, and healthcare-seeking behavior. Many hypotheses have been proposed, but it is not simple enough to be explained by a single factor.

Newly emerging in this context is the gender difference in "glial cells" that support nerve cells, rather than the nerve cells themselves.

The focus is on "supporting cells," not the "main players" of the brain

A research team from Saarland University in Germany compared post-mortem brain tissue from 72 Parkinson's disease patients and 24 individuals without the disease, examining which genes were actively working in various cells in the brain.

The research results were presented at the Federation of European Neuroscience Societies conference held in 2026.

When it comes to brain research, attention tends to focus on nerve cells, or neurons, which transmit information. However, the brain contains multiple glial cells that support neurons, supply nutrients, maintain the surrounding environment, and protect neural circuits.

In this study, astrocytes and oligodendrocytes were particularly highlighted for their gender differences.

Astrocytes are star-shaped cells that perform numerous tasks, such as supplying nutrients to nerve cells, recovering excess neurotransmitters, regulating ion concentrations, and participating in inflammatory responses. They are more like managers of the brain environment than mere "gap-filling cells."

On the other hand, oligodendrocytes create a structure called the "myelin sheath" around nerve fibers, which is essential for transmitting electrical signals quickly and accurately.

The research team found that there might be different activity patterns between genders in genes related to energy supply through mitochondria in astrocytes and genes related to the formation and maintenance of the myelin sheath in oligodendrocytes.

This suggests that when the male brain is under stress from Parkinson's disease, the way cells manage energy and protect nerve fibers may differ from that in females.

However, it is important to note that this does not mean it has been concluded that "men have weaker mitochondria" or "men's myelin sheaths are more fragile." What was shown is merely that there was a gender difference in gene activity observed in diseased brain tissue.

Whether this difference is a cause of onset, a result of disease progression, or reflects differences in drug treatment or living environment will need to be determined by future research.

"Cellular Stress" Common to Both Genders

The study also confirmed traces of cellular stress in multiple brain regions examined, regardless of gender.

Within cells, it is crucial for proteins to maintain their correct three-dimensional structure. When proteins deform due to heat, oxidative stress, aging, or pathological changes, cellular function is impaired.

This is where a group of proteins called "chaperones" come into play. Chaperones help damaged proteins maintain their correct shape and avoid abnormal aggregation.

In the current analysis, reactions related to chaperones were intensified in the brain cells of Parkinson's disease patients, suggesting that cells were attempting to respond to damage.

In Parkinson's disease, the abnormal accumulation of a protein called alpha-synuclein is a significant research focus. Cellular quality control, mitochondrial function, inflammation, and protein degradation systems influence each other, making it difficult to understand any single aspect in isolation.

The intriguing aspect of this study is that it suggests the possibility of gender differences in cellular energy supply and nerve fiber protection overlapping with common stress responses.

In other words, while there is a common pathology in Parkinson's disease, the brain's response to this stress may not be entirely the same between men and women.

Differences Not Only in "Susceptibility" but Also in "Symptom Presentation"

Gender differences are not only observed in the number of people who develop the disease.

A large-scale study examining 10,929 individuals with Parkinson's disease in Australia reported different trends in symptoms and past environmental exposures between men and women.

Among women, 70% reported pain, more than the 63% of men. Falls were reported by 45% of women and 41% of men, depression by 32% of women and 26% of men, and anxiety by 23% of women and 16% of men.

Among men, the proportion reporting memory changes was 67%, exceeding the 61% of women. REM sleep behavior disorder and sleep apnea were also more common in men, and impulsive behavior, particularly related to sexual conduct, was more noticeable in men.

However, these are average trends and should not be directly applied to individual patients. Some men suffer from pain, and some women have severe memory impairment. Symptoms and progression cannot be predicted based solely on gender.

Moreover, the Australian study was a cross-sectional survey based mainly on participants' self-reports, with less than 6% of those invited actually participating. Most participants were of European ancestry, and the same numbers may not apply to other regions or ethnic groups.

Nonetheless, the significance of showing that Parkinson's disease does not manifest in the same way for everyone from the experiences of over 10,000 patients is considerable.

Will Differences in Mitochondria and Myelin Lead to Treatment?

It is still unclear whether this research will directly lead to future treatments.

If it is confirmed that energy metabolism in specific cells tends to weaken more easily in men, the effectiveness of treatments targeting mitochondrial function or oxidative stress may vary depending on gender and the molecular type of the patient.

If there are differences in the maintenance of oligodendrocytes or myelin, new perspectives could be added to treatments that protect neural circuits, regulate inflammation, and organize interactions between cells.

Furthermore, there may be a shift from the current standard approach of administering the same drug in the same amount to choosing treatments based on a combination of each patient's gene activity, hormonal environment, age, symptoms, metabolism, and environmental exposure.

This is not simply about dividing drugs into "male" and "female" categories. Research on gender differences is not meant to fix patients into two groups but to help understand the diversity of the disease more intricately.

By using average gender differences as a starting point, researchers can investigate mitochondrial function, immune responses, hormones, gene regulation, and environmental factors behind them. The ultimate goal is to find diagnoses and treatments that suit each individual.

Not the Genes Themselves, but "How Genes Are Used"

The research team has also been focusing on epigenetic gender differences in Parkinson's disease.

Epigenetics refers to the mechanisms that regulate which genes are activated and which are silenced without changing the DNA sequence itself.

One representative mechanism is DNA methylation. By adding chemical markers to specific parts of DNA, the way genes are read changes.

In past analyses by the research team, it was found that the association between DNA methylation in the blood and the disease was stronger in women with early Parkinson's disease than in men.

Various factors such as aging, hormones, inflammation, diet, exercise, stress, and exposure to chemicals may be involved in these changes.

However, it is not appropriate to link this to personal responsibility by saying "the disease developed because of poor lifestyle habits." Many cases of Parkinson's disease are thought to occur due to a complex interplay of age, genetic predisposition, environment, and random cellular changes.

Pesticide exposure is also being studied as a risk factor, but not everyone exposed develops the disease, and those not exposed can also develop it. Further investigation is needed on the strength of causal relationships and the extent to which specific substances affect the disease.

"Expectations" and "Questions About Headlines" Intersect in SNS and Comment Sections

Multiple reactions were observed in the public comment section of the article reporting this research.

The most prominent were earnest voices from people who have experienced Parkinson's disease in their families. They were more interested in how the disease significantly changes the lives of the affected individuals and their families than in the gender difference in incidence rates, expressing a desire to know specific differences and applications to treatment.

On the other hand, there was criticism of the headline that gave the impression of discovering a "decisive factor," while the body of the article stated that the cause was not confirmed. Although the findings are an important clue, they do not fully explain the higher incidence rate in men with a single factor. Readers' questions serve as material for considering the balance between the strength of headlines in scientific reporting and the uncertainty of research results.

There were also voices focusing on the relationship between genetics and living environment. Some posts attempted to understand epigenetics as a mechanism by which diet, exercise, and stress change the way genes work, while others viewed it as a dichotomy between "is it ultimately genetics or lifestyle?"

In reality, current research indicates that it is not a matter of genetics or environment alone, but their interaction. Genetic predispositions can alter responses to the environment, and the environment can change how genes work.

Furthermore, the comparison of genders in the study sparked posts that shifted the topic from medical content to political and cultural debates about gender.

Here, researching biological gender differences and respecting individual gender identity and social roles are not inherently opposing. In medical research, it is necessary to distinguish between biological factors such as chromosomes, hormones, reproductive organs, body size, and drug metabolism, and social factors such as occupation, income, caregiving roles, and access to healthcare.

If the gender differences in disease are used as material for political victories or defeats, discussions on the diagnosis, treatment, and caregiving support truly needed by patients may be sidelined.

It is important to note that comments and posts on SNS are not public opinion surveys. There is a tendency for a small number of users with strong opinions to write extensively, and they do not represent the views of all patients, families, or society as a whole.

Limitations of the Research—Not "Answers" but "Where to Investigate Next"

There are clear limitations to this brain tissue study.

First, the brain tissue involved 72 Parkinson's disease patients and 24 controls, which is not sufficient to confirm gender differences in gene activity.

Second, in post-mortem brain research, it is difficult to distinguish differences that existed before the onset of the disease from those that resulted from years of disease progression.

Third, the medications used by patients during their lifetime, the duration of the disease, age at death, comorbidities, and living environment may have influenced gene activity.

Fourth, the research findings were presented at a conference stage and have not been published in a peer-reviewed academic journal as a completed paper. Until the analysis methods, statistical processing, and detailed patient backgrounds are disclosed and verified by other researchers, conclusions should be treated cautiously.

Nevertheless, the research has value.

Scientific progress occurs not by immediately presenting final answers but by gradually narrowing down "where to investigate next." The emergence of astrocyte energy metabolism and oligodendrocyte myelin maintenance as two candidate areas provides a concrete path for the next experiments and exploration of treatment targets.

Towards an Era of Not Considering Parkinson's Disease as "One Disease"

Parkinson's disease, even under the same diagnosis, can vary greatly in symptoms, age of onset, progression speed, and response to medication.

Some people primarily experience tremors, while others focus on slowness of movement or falls. Some experience constipation, sleep disorders, decreased sense of smell, depression, or pain before motor symptoms. Some have a strong relationship with genetic mutations, while others have no clear family history.

Considering this diversity, Parkinson's disease may be closer to a "syndrome" where multiple biological pathways ultimately converge into similar symptoms, rather than a single disease caused by a single factor.

The gender differences highlighted in this study are also a map to understanding that diversity.

Instead of just looking at statistics that men are more likely to develop the disease, investigating why brain cells respond differently between genders and why pain, cognition, sleep, and impulsivity manifest differently can lead to early diagnosis and personalized treatment.

However, gender is only one element in understanding a patient. True personalized medicine requires looking at age, genetic background, living environment, occupational history, comorbidities, social support, and the symptoms the individual finds most troubling.

Rather than deciding "this symptom because it's a man" or "this treatment because it's a woman," use average differences as clues to examine each individual's pathology in detail.

The most important message from this study is not that a single "decisive factor" explaining the risk of onset in men has been found.

It is that a new entry point has been found, suggesting that within the common stress responses in the brain of Parkinson's disease, there may be hidden gender differences in cells responsible for energy supply and nerve fiber protection.

・WELT. Main resource for confirming the overview of the current brain tissue study, the number of patients, and reactions in the comment section.
https://www.welt.de/gesundheit/article6a4cac2e1cbe5f3a786a95e4/warum-erkranken-maenner-haeufiger-an-parkinson-forscher-entdecken-entscheidenden-faktor.html

・Official announcement by the Federation of European Neuroscience Societies. Explanation of the study's objectives introduced at