Journal Article

DZNE-2026-00249

http://join2-wiki.gsi.de/foswiki/pub/Main/Artwork/join2_logo100x88.png Cerebrospinal Fluid Biomarkers of NLRP3 Pathway, Immune Dysregulation, and Neurodegeneration in Parkinson's Disease: A Meta-Analysis.

Marinescu, A.-M. ; Machado, V. ; Pagano, G. ; Muelhardt, N. M. ; Kustermann, T. ; Mracsko, E. Z. ; Brockmann, K.DZNE* ; Shariati, N. ; Anzures-Cabrera, J. ; Zinnhardt, B.

2026
Wiley New York, NY

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Please use a persistent id in citations: doi:10.1002/mds.70103

Abstract: The activation of the NOD-, LRR- and pyrin domain-containing protein 3 (NLRP3) inflammasome and associated immune dysregulation is one of the key pathological processes preceding and accompanying α-synuclein pathology, neuronal damage, and cell death in Parkinson's disease (PD). Biomarkers indicative of ongoing immune dysregulation could potentially serve as early indicators of disease activity and may support the development of novel immunomodulatory therapies.We performed a meta-analysis on 17 biomarkers related to specific components of the neuroinflammatory response in the cerebrospinal fluid of people with PD (PwP) and controls. We included studies that measured biomarkers related to NLRP3 inflammasome priming and activation (interleukin [IL]-1β, IL-18, IL-6, C-reactive protein, tumor necrosis factor [TNF]-α); reactive glial cells (soluble triggering receptor expressed on myeloid cells 2, chitinase 3-like-protein 1, glial fibrillary acidic protein, and s100); neurodegeneration (neurofilament light chain [NfL]); and other inflammatory mediators (interferon-ɣ, IL-2, IL-4, IL-8, IL-10, monocyte chemoattractant protein-1, chemokine C-X3-C motif chemokine ligand 1).Random-effects meta-analyses show markers downstream of the NLRP3 inflammasome priming and activation (IL-1β, IL-6, TNF-α), the astrocytic marker s100 calcium-binding protein B and neuroaxonal damage marker NfL are significantly increased in the cerebrospinal fluid (CSF) of PwP.The elevation in key downstream and general inflammatory mediators results is consistent with the hypothesized involvement of the NLRP3 inflammasome pathway and neurodegeneration in PD pathogenesis. These results highlight the potential use of CSF inflammatory markers and support further investigation into immunomodulatory strategies for PD. © 2025 The Author(s). Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.

Keyword(s): Humans (MeSH) ; Parkinson Disease: cerebrospinal fluid (MeSH) ; Parkinson Disease: immunology (MeSH) ; NLR Family, Pyrin Domain-Containing 3 Protein: cerebrospinal fluid (MeSH) ; NLR Family, Pyrin Domain-Containing 3 Protein: metabolism (MeSH) ; NLR Family, Pyrin Domain-Containing 3 Protein: immunology (MeSH) ; Biomarkers: cerebrospinal fluid (MeSH) ; Inflammasomes (MeSH) ; Biomarker ; CSF ; Inflammation ; NLRP3 ; Parkinson's disease ; NLR Family, Pyrin Domain-Containing 3 Protein ; Biomarkers ; NLRP3 protein, human ; Inflammasomes

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Contributing Institute(s):

1. Parkinson Genetics (AG Gasser)

Research Program(s):

1. 353 - Clinical and Health Care Research (POF4-353) (POF4-353)

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Database coverage:
; Clarivate Analytics Master Journal List ; Current Contents - Clinical Medicine ; Current Contents - Life Sciences ; DEAL Wiley ; Ebsco Academic Search ; Essential Science Indicators ; IF >= 5 ; JCR ; Nationallizenz ; SCOPUS ; Science Citation Index Expanded ; Web of Science Core Collection

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