Peripheral inflammation may drive brain damage in rare neurological disorder: NIMHANS study

A study by researchers at the National Institute of Mental Health and Neuro-Sciences (NIMHANS) has found that peripheral inflammation — inflammation occurring outside the brain — may play a significant role in triggering brain inflammation and neurodegeneration in Progressive Supranuclear Palsy (PSP), a rare neurological disorder that currently has no disease-modifying treatment.

The findings, published in the journal Frontiers in Immunology, offer fresh insights into how the disease develops. They also raise the possibility of identifying blood-based biomarkers that could improve diagnosis and potentially guide future therapeutic strategies, the researchers said.

Understanding PSP

PSP is a progressive neurodegenerative disorder characterised by loss of balance, difficulty in walking, swallowing and speaking, as well as impairment of eye movements. Because many of its early symptoms overlap with Parkinson's disease, it is frequently misdiagnosed during the initial stages. Although previous research has suggested that abnormal immune responses contribute to neurodegenerative diseases, the mechanisms through which inflammation outside the brain influences brain pathology have remained poorly understood.

The study, led by Monojit Debnath, professor of human genetics at NIMHANS, sought to bridge this knowledge gap by investigating inflammatory pathways both within the central nervous system and in the peripheral immune system.

Multi-pronged investigation

The researchers examined three major inflammatory pathways — the NLRP3 inflammasome, the NF-κB pathway, and the Th17 pathway — all of which are known to regulate immune responses. Using a multi-pronged approach, the team analysed inflammatory markers in peripheral blood and cerebrospinal fluid while simultaneously employing PET-MRI imaging to assess inflammation in the brain. The combined analysis demonstrated a clear association between inflammation in the peripheral immune system and neuroinflammation in patients with PSP.

The findings add to a growing body of evidence suggesting that several neurodegenerative disorders may not originate solely within the brain but may also involve immune processes occurring elsewhere in the body.

Hope for better diagnosis

Explaining the significance of the findings, Dr. Debnath told The Hindu that the study is the first to establish a direct connection between peripheral inflammation and brain inflammation in patients with PSP. “Finding a definite and reliable biomarker in peripheral blood is the need of the hour for the accurate diagnosis of various neurodegenerative diseases, including PSP. Our study raises hope in that direction,” he said.

Dr. Debnath said the findings strengthen the hypothesis that the immune system outside the brain plays an active role in the disease process, especially in the ongoing neurodegeneration.

Ravi Yadav, professor of neurology at NIMHANS and a senior author of this study, emphasised that understanding the relationship between systemic inflammation and brain pathology could help researchers develop simpler and more accurate diagnostic tools based on blood samples. This reduces dependence on neurological investigations, which do not have 100% diagnostic accuracy and sensitivity, Dr. Yadav said.

Disease mechanisms

The researchers said PSP is caused by degeneration of nerve cells in brain regions that control movement and cognition and is characterised by abnormal accumulation of tau protein. While rogue immune cells are believed to contribute to this process, the factors that trigger these abnormal immune responses have remained unclear. The present study suggests that inflammatory changes occurring in the peripheral immune system may influence immune activity within the brain, thereby contributing to neuronal damage and disease progression.

Further studies involving larger patient groups would be required to validate the findings and determine whether the identified inflammatory pathways could be targeted for future therapies, Dr. Debnath said.

The study adds to a growing body of research that could eventually lead to less invasive diagnostic methods and new avenues for treating PSP and other neurodegenerative conditions.