Clinical Phenotypes of Progressive Supranuclear Palsy—The Differences in Interleukin Patterns

Abstract

Progressive supranuclear palsy (PSP) is an atypical parkinsonian syndrome based on tau pathology; its clinical phenotype differs, but PSP with Richardson’s syndrome (PSP-RS) and the PSP parkinsonism predominant (PSP-P) variant remain the two most common manifestations. Neuroinflammation is involved in the course of the disease and may cause neurodegeneration. However, an up-to-date cytokine profile has not been assessed in different PSP phenotypes. This study aimed to evaluate possible differences in neuroinflammatory patterns between the two most common PSP phenotypes. Serum and cerebrospinal fluid (CSF) concentrations of interleukin-1 beta (IL-1β) and IL-6 were analyzed using enzyme-linked immunosorbent assay (ELISA) kits in 36 study participants—12 healthy controls and 24 patients with a clinical diagnosis of PSP-12 PSP-RS and 12 PSP-P. Disease duration among PSP patients ranged from three to six years. All participants underwent basic biochemical testing, and neutrophil-to-lymphocyte ratio (NLR) and platelet-to-lymphocyte ratio (PLR) values were calculated. Due to a lack of neuropathological examinations, as all patients remain alive, total tau levels were assessed in the CSF. Tau levels were significantly higher in the PSP-P and PSP-RS groups compared to the healthy controls. The lowest concentrations of serum and CSF interleukins were observed in PSP-RS patients, whereas PSP-P patients and healthy controls had significantly higher interleukin concentrations. Furthermore, there was a significant correlation between serum IL-6 levels and PLR in PSP-RS patients. The results indicate the existence of distinct neuroinflammatory patterns or a neuroprotective role of increased inflammatory activity, which could cause the differences between PSPS phenotypes and clinical course. The causality of the correlations described requires further studies to be confirmed.

Association analysis of dopaminergic degeneration and the neutrophil-to-lymphocyte ratio in Parkinson’s disease

“…Brodacki et al reported abnormal elevations in IL2, IL6, and TNF-α levels in PD patients, suggesting a potential link between peripheral inflammation and PD ( Brodacki et al, 2008 ). Furthermore, peripheral inflammation may be also associated with other atypical parkinsonisms and neurodegenerative diseases, including Alzheimer’s disease (AD) and PSP ( Akiyama et al, 2000 ; Madetko-Alster et al, 2023 ). However, the specific molecular mechanisms remain largely unclear.…”

The potential significance of hepcidin evaluation in progressive supranuclear palsy

“…PSP‐P is a more favorable clinical entity in the PSP spectrum; however certain works point out that it may be a type of a slower clinical deterioration leading to the same outcome as PSP‐RS. Glial cell‐line‐derived neurotrophic factor, interleukin‐1 and Interleukin‐6 were indicated as factors possibly impacting the evolution of PSP; however, it remains unknown whether the modulation of these elements is a mechanism that may oppose the primary neurodegeneration (Alster et al., 2024 ; Madetko‐Alster et al., 2023 ). Other works evaluating possible overlaps between neurodegeneration and inflammatory mechanisms in the pathogenesis of PSP did not indicate the two major subtypes or are based on nonspecific factors as neutrophil‐to‐lymphocyte ratio (Brodacki et al., 2008 ; Inci et al., 2020 ; Nübling et al., 2017 ; Rydbirk et al., 2019 ).…”

Significance of dysautonomia in Parkinson’s Disease and atypical parkinsonisms

“…The fact that decreased HRV is linked with PSP-RS and MSA, but not with PSP-P, may suggest that subtypes of PSP may be associated with different mechanisms affecting the autonomic nervous system [19]. Previous evaluations of HRV, though lacking the division into PSP subtypes, revealed ambiguous results, which could be partly caused by the small number of patients [20].…”