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@ARTICLE{Marinescu:285472,
author = {Marinescu, Alina-Măriuca and Machado, Venissa and Pagano,
Gennaro and Muelhardt, Nicoletta Milani and Kustermann,
Thomas and Mracsko, Eva Zsuzsanna and Brockmann, Kathrin and
Shariati, Nima and Anzures-Cabrera, Judith and Zinnhardt,
Bastian},
title = {{C}erebrospinal {F}luid {B}iomarkers of {NLRP}3 {P}athway,
{I}mmune {D}ysregulation, and {N}eurodegeneration in
{P}arkinson's {D}isease: {A} {M}eta-{A}nalysis.},
journal = {Movement disorders},
volume = {41},
number = {2},
issn = {0885-3185},
address = {New York, NY},
publisher = {Wiley},
reportid = {DZNE-2026-00249},
pages = {466 - 477},
year = {2026},
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.},
keywords = {Humans / Parkinson Disease: cerebrospinal fluid / Parkinson
Disease: immunology / NLR Family, Pyrin Domain-Containing 3
Protein: cerebrospinal fluid / NLR Family, Pyrin
Domain-Containing 3 Protein: metabolism / NLR Family, Pyrin
Domain-Containing 3 Protein: immunology / Biomarkers:
cerebrospinal fluid / Inflammasomes / Biomarker (Other) /
CSF (Other) / Inflammation (Other) / NLRP3 (Other) /
Parkinson's disease (Other) / NLR Family, Pyrin
Domain-Containing 3 Protein (NLM Chemicals) / Biomarkers
(NLM Chemicals) / NLRP3 protein, human (NLM Chemicals) /
Inflammasomes (NLM Chemicals)},
cin = {AG Gasser},
ddc = {610},
cid = {I:(DE-2719)1210000},
pnm = {353 - Clinical and Health Care Research (POF4-353)},
pid = {G:(DE-HGF)POF4-353},
typ = {PUB:(DE-HGF)16},
pubmed = {pmid:41317029},
pmc = {pmc:PMC12951271},
doi = {10.1002/mds.70103},
url = {https://pub.dzne.de/record/285472},
}