Barcelona, Spain: New research presented today (Wednesday) at the Federation of European Neuroscience Societies (FENS) Forum 2026 [1] has discovered some of the genetic changes in brain cells that may help to explain why more men than women develop Parkinson's disease.
Parkinson's disease (PD) is a condition in which parts of the brain become progressively damaged over many years. It affects approximately 9.4 million people worldwide and it is becoming increasingly prevalent, especially as populations age. Around 90% of cases are thought to be caused by a combination of genetic variations and environmental and lifestyle factors. PD is 1.5- to 2-fold more common in men than women, but the reasons for this difference are not clear. Men also experience a faster decline in their thinking abilities and faster progression of difficulties with everyday living.
Dr Julia Schulze-Hentrich, a professor in the Genetics and Epigenetics Department and affiliated with the Center for Gender-Specific Biology and Medicine (CGMB) at Saarland University, Germany, told the FENS Forum: "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."
In earlier work [2], Professor Schulze-Hentrich and colleagues had studied blood samples from agricultural workers, including 71 people with early PD and 147 healthy controls. They found that women with PD had changes to DNA methylation in 69 regions of the genome, compared to only two in men. DNA methylation doesn't change genes, but works like a dimmer switch to turn the activity of genes up or down.
"These findings suggested that a person's genetic make-up 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," she said.
In her new research presented today, Prof. Schulze-Hentrich set out to understand the mechanisms that might be playing a role in the different DNA methylation patterns she had seen in men and women and their associations with PD. The researchers looked at post-mortem brain samples from 73 people with PD (28 women and 45 men) and compared them with samples from a control group of 24 people without PD (9 women and 15 men).
"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," she said.
Neurons are the brain's communication nerve cells, while astrocytes, oligodendrocytes and microglia are glial nerve cells, which provide support and maintenance for the neurons.
The researchers found that in astrocytes, the activity of genes linked to mitochondria (the cell's energy producers) was different between sexes. In oligodendrocytes, the activity of genes involved in making and maintaining the protective coating around nerve fibres (myelin) also differed between sexes. These differences occurred regardless of what region of the brain they were in.
"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 personalised treatments rather than treating all patients with PD as biologically identical," said Prof. Schulze-Hentrich.
"Most importantly, our results indicate that 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. 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 under-report or pool sex-specific outcomes.
"For patients, the main benefit is more personalised 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."
The discovery of how different cells in the brain function differently between sexes, both healthy and diseased, is a strength of the study and fills a gap left by studies that have focussed just on neurons and males. A limitation is the small number of samples investigated. Prof. Schulze-Hentrich said that a coordinated effort was needed to improve this and investigate greater numbers of samples, stratified by sex.
"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," she concluded.
Professor Christina Dalla from the National and Kapodistrian University of Athens, Greece, is chair of the FENS Forum communication committee and was not involved in the research. she said: "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."
