Temporal associations of CGRP-related inflammatory pathway biomarkers in Synuclein-Associated Neurodegenerative Disorders (SAND)

Authors

ATHANASIA
Panagiota Petrou
Evaggelia Livaniou
Vincenzo Donadio
Alex Incensi
Margarita Maimani
Julie Pitman
Ζοι Devenopoulou
Anastasia Mantzou
Ioannis Stavropoulos
Konstantina Sykara
Elissaios Karageorgiou

Abstract

Aim: This study investigates the role of calcitonin gene-related peptide (CGRP) and its related inflammatory biomarkers in individuals with Synuclein-Associated Neurodegenerative Disorders (SAND), encompassing conditions like Parkinson’s disease (PD) and Multiple System Atrophy (MSA). Given CGRP’s known anti-inflammatory and neuroprotective properties demonstrated in vitro and in animal models, we aimed to explore its association with inflammatory pathways in humans across different circadian stages.

Material and Methods: We analyzed plasma levels of biomarkers such as CGRP, NLRP3 inflammasome components, IL-1β, and IL-18, along with hair cortisol, in 15 participants (7 with SAND, 8 controls). Blood samples were collected before and after overnight sleep studies, and correlations between these markers were assessed using non-parametric tests.

Results: Across groups, all plasma biomarkers showed significant correlations before and after sleep. In controls, strong temporal associations within the CGRP pathway were observed, particularly between pre-sleep IL18, post-sleep CGRP, and hair cortisol, driven primarily by control group variance. These biomarkers also related to clinical features such as cognition and motor function, with notable associations between inflammatory markers and cognitive scores. In the SAND group, fewer biomarker correlations were found, with pre-sleep NLRP3 correlating with hair cortisol. Only pre-sleep CGRP and IL18 levels significantly differed between groups, suggesting disease-specific alterations in circadian biomarker patterns.

Conclusions: The above highlights that temporal fluctuations of inflammatory biomarkers differ in patients with SAND compared to controls. By extension, the lack of association of CGRP to these inflammatory markers in patients, but its association in controls suggests that under healthy conditions CGRP exerts some control over the inflammatory cascade, but its absence allows for stronger inflammatory biomarker co-expressions at 4-5 years of disease onset.