Scientists have identified sex-specific differences in gene activity within brain cells that may help explain why Parkinson’s disease affects men more frequently than women.
Men are 1.5 to 2 times more likely than women to develop Parkinson’s disease, yet the biological reasons remain poorly understood. New research suggests that differences in gene activity within the brain’s support cells may help explain why the condition affects the sexes differently.
The findings, presented at the Federation of European Neuroscience Societies (FENS) Forum 2026, are based on brain tissue from 73 people with Parkinson’s disease (28 women and 45 men) and 24 people without the condition (9 women and 15 men). Researchers examined five brain regions, identifying cellular changes shared by both sexes as well as distinct patterns in men and women.
Brain Support Cells Reveal Sex-Specific Differences
The strongest differences appeared in two types of glial cells, which support and protect neurons. In astrocytes, gene activity related to mitochondria, the structures that produce cellular energy, differed between sexes. In oligodendrocytes, researchers identified differences involving genes responsible for producing and maintaining myelin, the protective coating surrounding nerve fibers. These patterns appeared across the brain regions studied.
Professor Julia Schulze-Hentrich of Saarland University in Germany, who led the research, explained: “We looked at differences in gene expression individually in all cells of the brain – neurons, astrocytes, oligodendrocytes and microglia – in healthy brains and in PD brains in men and women. We studied five brain regions and found that PD causes common changes in the brain, regardless of sex. All these cells in the five regions, showed signs of being under stress. They switched on proteins that help damaged proteins fold correctly, called ‘chaperones’. However, we also found important differences between men and women in gene activity in some cells and some brain regions.”
“This shows that PD triggers some shared ‘stress responses’ in everyone’s brain cells, but also there are differences between men and women at the cellular level, especially in how the brain ‘support’ cells manage energy and protect nerve connections. Our findings help to explain why symptoms and disease progression in Parkinson’s differ between men and women. Eventually, they may lead to more personalized treatments rather than treating all patients with PD as biologically identical,” said Prof. Schulze-Hentrich.
Why Parkinson’s Affects Men More Often
Parkinson’s disease causes progressive brain damage and affects approximately 9.4 million people worldwide. About 90% of cases are thought to involve a combination of genetic variation and environmental or lifestyle influences. Men not only develop the disease more frequently but also tend to experience faster cognitive decline and worsening difficulties with everyday activities.
“The higher prevalence of Parkinson’s disease in men suggests that sex-dependent biology may influence vulnerability. Therefore, studying sex differences may help identifying disease mechanisms that would be hidden in analyses that pool men and women together,” said Prof. Schulze-Hentrich, who is affiliated with Saarland University’s Center for Gender-Specific Biology and Medicine (CGMB).
Earlier Research Linked Parkinson’s to DNA Changes
The investigation builds on an earlier study involving 71 agricultural workers with early Parkinson’s and 147 healthy participants. Researchers found changes in DNA methylation across 69 genomic regions in women with Parkinson’s, compared with just two in men. DNA methylation regulates gene activity without altering the underlying DNA sequence, functioning much like a dimmer switch.
“These findings suggested that a person’s genetic makeup influences these DNA methylation changes, and that interaction with environmental exposures, such as to pesticides, may also contribute to the development of Parkinson’s disease,” Prof. Schulze-Hentrich said.
The new study extended this work by examining gene expression in individual types of brain cells. Although it identified differences associated with biological sex, it did not establish that those differences directly cause the higher rate of Parkinson’s in men.
Toward More Personalized Parkinson’s Care
The study’s relatively small sample size limits its conclusions, and larger investigations are needed. The findings also reinforce the need to examine men and women separately in Parkinson’s research, which has historically focused heavily on neurons and male subjects.
“Most importantly, our results indicate that it is crucial to recognize that biology varies between the sexes in PD research and that, wherever possible, researchers should analyze data separately in males and females instead of pooling everyone together. This is crucial to see whether an association, effect or outcome differs by sex. It also helps identify gaps in evidence because many studies still underreport or pool sex-specific outcomes.
“For patients, the main benefit is more personalized care, as sex-specific analysis can help clinicians predict which symptoms are more likely, monitor problems earlier, and choose treatments that fit a patient’s risk profile better.”
A new German research initiative aims to investigate how sex-related differences in glial cells affect neurological disease.
“Investigating how male- and female-specific glial responses shape vulnerability, progression and treatment response is rarely done in a systematic and coordinated way. Therefore, the German Research Foundation (DFG) Priority Programme ‘SEX and GLIA’ starting in the autumn of 2026 will bring together physiologists with functional geneticists and computational biologists to uncover a largely hidden layer of sex-biased biology that previous studies often ignored,” Prof. Schulze-Hentrich concluded.
Understanding the Role of Brain Support Cells
Professor Christina Dalla of the National and Kapodistrian University of Athens, Greece, who chairs the FENS Forum communication committee and was not involved in the research, highlighted how the findings build on earlier investigations of environmental exposures.
“Although we have known for some time that there are higher rates of Parkinson’s disease in men than in women, it is interesting to see how Professor Schulze-Hentrich and her colleagues have built on their earlier work studying the impact of pesticides on agricultural workers to investigate the changes that occur at the cellular level and to understand the mechanisms underlying the development of Parkinson’s disease.
“Their findings show that although some changes in genetic activity are the same in both sexes, there are others that only occur in men, or in women. This is an important finding because it shows that there are differences in glial cells, the ‘support’ cells in the brain that are associated with the onset of the disease, and that these could interact with other factors such as sex, hormones, or social or environmental exposures.”
Meeting: FENS Forum 2026
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