New Study Links Immune System to Higher Parkinson’s Risk in Men
A groundbreaking study from the La Jolla Institute for Immunology (LJI) has identified a key factor that may explain why men are twice as likely as women to develop Parkinson’s disease (PD). The research, published in The Journal of Clinical Investigation, reveals that the immune system may mistakenly attack a protein in brain cells, accelerating the onset of the disease.
A Hidden Trigger for Parkinson’s Disease?
The study focuses on a protein called PINK1, which is crucial for maintaining the health of mitochondria—tiny structures that power brain cells. In people with Parkinson’s, certain immune cells, known as T cells, appear to misidentify PINK1 as a threat and launch an attack.
“We found that some Parkinson’s patients have T cells that mistakenly see PINK1 as a red flag,” said Dr. Alessandro Sette, senior author of the study. “This immune response may be a component of why we see a sex difference in Parkinson’s disease.”
Why Are Men More Affected?
One of the most striking findings is the gender disparity in immune response. The study showed that men with Parkinson’s have a six-fold increase in PINK1-specific T cells compared to healthy men. Women with Parkinson’s, by contrast, showed only a 0.7-fold increase.
“The sex-based differences in T cell responses were very, very striking,” said Sette.
This could explain why men are diagnosed with Parkinson’s at much higher rates than women. The researchers suspect that female hormones like estrogen may help suppress this autoimmune attack, potentially providing a protective effect in premenopausal women.
A New Path for Diagnosis and Treatment
These findings suggest that PINK1-targeting T cells could serve as a biomarker for early detection of Parkinson’s, allowing for diagnosis before severe symptoms appear.
“We could potentially develop therapies to block these T cells, now that we know why they are targeting the brain,” said Dr. Cecilia Lindstam Arlehamn, co-lead author of the study.
This discovery builds on previous research linking Parkinson’s to an autoimmune response against another protein, alpha-synuclein, which forms harmful clumps in the brains of PD patients. However, not all Parkinson’s patients exhibit this alpha-synuclein response, suggesting that multiple immune system triggers may contribute to the disease.
Looking Ahead
The LJI research team is now expanding its studies to analyze other potential autoimmune targets in Parkinson’s disease.
“We need to perform a more global analysis of the disease progression and sex differences—considering all the different antigens, disease severities, and time since disease onset,” said Sette.
With Parkinson’s affecting more than 10 million people worldwide, these findings mark a significant step toward understanding the disease’s root causes and developing targeted treatments that could slow or even prevent its progression.
For more details, visit the full study in The Journal of Clinical Investigation here.
