Brain Cell Changes Reveal Why Parkinson's Disease Affects More Men Than Women
核心洞察
New research presented at the FENS Forum 2026 uncovers sex-specific genetic changes in brain cells that may explain why Parkinson's disease (搜索) is 1.5- to 2-fold more common in men than women.
The study found that while both sexes share common stress responses in brain cells, astrocytes and oligodendrocytes show key differences in gene activity related to mitochondrial function and myelin maintenance.
Women with Parkinson's showed DNA methylation (搜索) changes in 69 genomic regions compared to only two in men, suggesting genetic makeup strongly influences epigenetic patterns.
A new study presented at the Federation of European Neuroscience Societies (FENS) Forum 2026 in Barcelona, Spain, has uncovered genetic changes in brain cells that may help explain why Parkinson's disease (搜索) is significantly more prevalent in males. The research, led by Professor Julia Schulze-Hentrich of Saarland University (搜索), Germany, reveals that sex-dependent differences in gene activity within glial cells — particularly astrocytes and oligodendrocytes — could underlie the observed disparity in disease susceptibility and progression.
Parkinson's disease (搜索) is the second-most prevalent neurodegenerative condition, affecting approximately 1% of people aged over 60 and an estimated 9.4 million people worldwide. Males are around 1.5 to 2 times more likely to develop the condition than females, and men also experience faster cognitive decline and more rapid progression of difficulties with everyday living. With cases projected to reach approximately 9 million by 2030, understanding the biological mechanisms driving these sex differences has become increasingly urgent.
From Blood to Brain: Building on Earlier Epigenetic Findings
The current study builds on Professor Schulze-Hentrich's earlier research involving blood samples from agricultural workers, which included 71 people with early Parkinson's disease (搜索) and 147 healthy controls. That work revealed a striking disparity: women with Parkinson's had changes to DNA methylation (搜索) in 69 regions of the genome, compared to only two regions in men. DNA methylation, the most well-studied form of epigenetic modification, does not alter the DNA code itself but acts like a dimmer switch to turn gene activity up or down.
"These findings suggested that a person's genetic make-up influences these DNA methylation (搜索) changes, and that interaction with environmental exposures, such as to pesticides, may also contribute to the development of Parkinson's disease (搜索)," Schulze-Hentrich explained.
Investigating Brain Cells Across Five Regions
To understand the mechanisms behind these differing methylation patterns, Schulze-Hentrich and her colleagues analyzed post-mortem brain samples from 73 people with Parkinson's disease (搜索) (28 women and 45 men) and compared them with samples from a control group of 24 individuals without the condition (9 women and 15 men). The researchers measured differences in gene expression across all brain cell types — neurons, astrocytes, oligodendrocytes, and microglia — in five distinct brain regions.
The analysis revealed that Parkinson's disease (搜索) triggers 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,'" Schulze-Hentrich said.
Sex-Specific Differences in Glial Cells
Beyond these shared stress responses, the team identified important differences in gene activity between males and females in specific cell types. In astrocytes, the activity of genes linked to mitochondria — the cell's energy-producing organelles — differed between sexes. In oligodendrocytes, the activity of genes responsible for creating and maintaining the myelin sheath, the protective coating around nerve fibers essential for signal transduction, also varied by sex. These differences occurred regardless of which brain region was examined.
"This shows that Parkinson's 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," Schulze-Hentrich noted. "Our findings help to explain why symptoms and disease progression in Parkinson's differ between men and women."
Toward Personalized Treatment Approaches
The researchers emphasized that their results underscore the importance of analyzing data separately by sex in Parkinson's research. "It is crucial to recognise that biology varies between the sexes in PD research and that, wherever possible, researchers should analyse data separately in males and females instead of pooling everyone together," Schulze-Hentrich stated. "This is crucial to see whether an association, effect or outcome differs by sex."
For patients, the main benefit would be more personalized care. Sex-specific analysis could help clinicians predict which symptoms are more likely, monitor problems earlier, and choose treatments that better fit a patient's risk profile. "Eventually, they may lead to more personalised treatments rather than treating all patients with PD as biologically identical," Schulze-Hentrich concluded.
Study Strengths, Limitations, and Future Directions
A key strength of the study is its focus on glial cells across both sexes, filling a gap left by previous research that concentrated primarily on neurons and males. However, the small number of samples investigated represents a limitation. To address this, a coordinated effort is underway: the German Research Foundation (DFG) Priority Programme 'SEX and GLIA,' launching in autumn 2026, will bring together physiologists, functional geneticists, and computational biologists to systematically investigate how male- and female-specific glial responses shape vulnerability, progression, and treatment response in Parkinson's disease (搜索).
Professor Christina Dalla from the National and Kapodistrian University of Athens, Greece, who chairs the FENS Forum communication committee and was not involved in the research, commented: "Although we have known for some time that there are higher rates of Parkinson's disease (搜索) 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."