Peripheral and central inflammation in progressive supranuclear palsy syndrome: an immunological and imaging neuroinflammation study.

INTRODUCTION

Neuroinflammation plays an important role in the pathobiology of Progressive Supranuclear Palsy Syndrome (PSP-S). However, it is not adequately known whether peripheral inflammation correlates to neuroinflammation in PSP-S. This study aimed to examine a link between peripheral and brain inflammation in PSP-S by integrating blood and cerebrospinal fluid (CSF) inflammatory profile and Positron Emission Tomography (PET)-Magnetic Resonance Imaging (MRI) (PET-MRI).

METHODS

Fifty-six PSP-S patients and equal number of healthy controls were recruited. Plasma Th17 pathway cytokine (IL-6, IL-1β, IL-4, IL-10, IL-17A, IL-17F, IL-21, IL-22, IL-23, IL-25, IL-31, IL-33, IFN-γ, sCD40L, and TNF-α) levels were measured in all the study participants. CSF levels of these cytokines were measured only in PSP-S patients. The expressions of NF-κB (Nfkb1, and Nfkb2), inflammasome (Nlrp3, Casp1, and Il18), Th17 (Il1b, Il6, Il17, Tnfa, Il22, Il23, Rorc, and Stat3) and anti-inflammatory (Tgfb, and Il10) genes were quantified in all the study participants. PET-MRI was carried out in a subset of PSP-S patients (n=12) and eleven disease controls (Parkinson's Disease=7, and Multiple System Atrophy=4).

RESULTS

Inflammasome (Casp1 and Il18), NF-κB (Nfkb1) and inflammatory (Il1b and Il6) genes were upregulated in PSP-S patients. Plasma IL-1β, IL-6, IL-17A, and IL-17F levels were significantly elevated in PSP-S patients. IL-1β levels significantly correlated between plasma and CSF. PET-MRI indicated neuroinflammation in several brain regions of PSP-S patients.

CONCLUSION

Both systemic inflammation and neuroinflammation are evident in PSP-S. The positive correlation of higher plasma IL-1β levels with neuroinflammation provides preliminary evidence towards the influence of specific peripheral inflammatory molecule on neuroinflammatory basis of PSP-S. The altered immune elements of the current study further reinforce the pathogenic relevance of immune-inflammatory pathways in PSP-S pathobiology.