TY  - JOUR
AU  - Marinescu, Alina-Măriuca
AU  - Machado, Venissa
AU  - Pagano, Gennaro
AU  - Muelhardt, Nicoletta Milani
AU  - Kustermann, Thomas
AU  - Mracsko, Eva Zsuzsanna
AU  - Brockmann, Kathrin
AU  - Shariati, Nima
AU  - Anzures-Cabrera, Judith
AU  - Zinnhardt, Bastian
TI  - Cerebrospinal Fluid Biomarkers of NLRP3 Pathway, Immune Dysregulation, and Neurodegeneration in Parkinson's Disease: A Meta-Analysis.
JO  - Movement disorders
VL  - 41
IS  - 2
SN  - 0885-3185
CY  - New York, NY
PB  - Wiley
M1  - DZNE-2026-00249
SP  - 466 - 477
PY  - 2026
AB  - 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.
KW  - Humans
KW  - Parkinson Disease: cerebrospinal fluid
KW  - Parkinson Disease: immunology
KW  - NLR Family, Pyrin Domain-Containing 3 Protein: cerebrospinal fluid
KW  - NLR Family, Pyrin Domain-Containing 3 Protein: metabolism
KW  - NLR Family, Pyrin Domain-Containing 3 Protein: immunology
KW  - Biomarkers: cerebrospinal fluid
KW  - Inflammasomes
KW  - Biomarker (Other)
KW  - CSF (Other)
KW  - Inflammation (Other)
KW  - NLRP3 (Other)
KW  - Parkinson's disease (Other)
KW  - NLR Family, Pyrin Domain-Containing 3 Protein (NLM Chemicals)
KW  - Biomarkers (NLM Chemicals)
KW  - NLRP3 protein, human (NLM Chemicals)
KW  - Inflammasomes (NLM Chemicals)
LB  - PUB:(DE-HGF)16
C6  - pmid:41317029
C2  - pmc:PMC12951271
DO  - DOI:10.1002/mds.70103
UR  - https://pub.dzne.de/record/285472
ER  -