Men's and Women's Brains Age Differently: New Insights into Parkinson's Disease

A new study has identified sex-specific changes in gene activity within brain cells that may help explain why Parkinson's disease is more common in men than in women. The findings were presented at FENS Forum 2026, the international meeting of the Federation of European Neuroscience Societies, as reported by News Medical.

Parkinson's disease is a progressive neurodegenerative disorder in which specific regions of the brain gradually deteriorate. It currently affects an estimated 9.4 million people worldwide, and the number of cases continues to rise as the global population ages. Approximately 90% of cases are believed to result from a combination of genetic susceptibility, environmental exposures, and lifestyle factors.

It has long been recognized that Parkinson's disease occurs 1.5 to 2 times more frequently in men than in women. Men also tend to experience more rapid cognitive decline and greater impairment in performing everyday activities. However, the biological basis for these differences has remained largely unknown.

Professor Julia Schulze-Hentrich of Saarland University in Germany previously investigated blood samples from agricultural workers, including 71 individuals with early-stage Parkinson's disease and 147 healthy controls. That study identified changes in DNA methylation—an epigenetic mechanism that regulates gene activity without altering the DNA sequence itself. Women with Parkinson's disease exhibited methylation changes at 69 genomic sites, whereas only two such changes were detected in men.

In the new study, the researchers examined postmortem brain tissue from 73 patients with Parkinson's disease (28 women and 45 men) and compared it with brain samples from 24 individuals without the disease.

The team analyzed gene expression across several major brain cell types, including neurons, astrocytes, oligodendrocytes, and microglia. Regardless of sex, all cell types showed evidence of cellular stress, characterized by increased production of molecular chaperone proteins, which help repair or refold damaged proteins.

However, the researchers also identified important sex-specific differences. In astrocytes, which provide structural and metabolic support to neurons, they observed differences in the activity of genes involved in mitochondrial function, the process responsible for cellular energy production. In oligodendrocytes, gene activity differed in pathways responsible for the formation and maintenance of myelin, the protective sheath surrounding nerve fibers.

The researchers believe these biological differences may influence the brain's vulnerability to disease, the rate of disease progression, and patients' responses to treatment. The findings suggest that Parkinson's disease should not be viewed as a uniform condition and that biological sex may play an important role in its underlying mechanisms.

The authors emphasize the importance of analyzing data from men and women separately rather than combining them into a single group. Such an approach could ultimately contribute to the development of more personalized strategies for diagnosing and treating Parkinson's disease.

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