Evidence map›Paper›PMID 41257354›Full record

ArticleMovement disorders : official journal of the Movement Disorder Society2026

Parkinson's-Linked LRRK2 and GBA1 Mutations Modulate the Peripheral Immune Response to Pseudomonas aeruginosa.

Julian R Mark, Hannah A Staley, Ann M Titus, Julian Agin-Liebes, Alicia Garrido, Laura Hughes, Nicolas Dzamko, Rebecca L Wallings, Malú Gámez Tansey

Abstract read
In one paragraph

Article in Movement disorders : official journal of the Movement Disorder Society, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 2 papers.

0numbers the graph read from it
0cells of the map it votes in
2citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

2 citing papers in PubMed.

  1. Review
  2. Review
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

9 authors.

Julian R MarkDepartment of Neuroscience, University of Florida, College of Medicine, Gainesville, FL, USA.
Hannah A StaleyTrinity College of Arts and Sciences, Duke University, Durham, NC, USA.
Ann M TitusDepartment of Neuroscience, University of Florida, College of Medicine, Gainesville, FL, USA.
Julian Agin-LiebesDepartment of Neurology, Columbia University Irving Medical Center, New York, NY, USA.
Alicia GarridoParkinson's Disease and Movement Disorders Unit Institut Clínic de Neurociències Hospital Clinic de Barcelona, Barcelona, Spain.
Laura HughesMedicine and Health, University of Sydney, Sydney, NSW, Australia.
Nicolas DzamkoMedicine and Health, University of Sydney, Sydney, NSW, Australia.ORCID https://orcid.org/0000-0002-9121-0294
Rebecca L WallingsDepartment of Neuroscience, University of Florida, College of Medicine, Gainesville, FL, USA.
Malú Gámez TanseyDepartment of Neuroscience, University of Florida, College of Medicine, Gainesville, FL, USA.ORCID https://orcid.org/0000-0002-1719-4708

Funding

Networking and Expanding Undergraduate Research on the Neurobiology of Aging to Advance DiversityR25AG076396 · NIA · UNIVERSITY OF FLORIDA · PI ABISAMBRA, JOSE FRANCISCO, ALVINA, KARINA · 2022 to 2024
$1.1M
Michael J. Fox Foundation for Parkinson's Research 008714Michael J. Fox Foundation for Parkinson's Research 023925NIH HHS R25AG076396Shake It Up Australia Foundation 16778
6 · The paper itself

Abstract

backgroundPeripheral disease mechanisms such as immune dysregulation may contribute to Parkinson's disease (PD). To investigate interactions between common PD mutations and immune responses to environmental pathogens, we studied responses to Pseudomonas aeruginosa (P. aeruginosa) in peripheral blood mononuclear cells (PBMCs) from PD patients with leucine-rich repeat kinase 2 (LRRK2) mutations, GBA1 mutations, and idiopathic disease (iPD) relative to neurologically healthy controls (NHC).

objectivesThe goal was to test the hypothesis that LRRK2 and GBA modify the human peripheral immune response to bacteria, specifically P. aeruginosa, based on prior animal studies involving Lrrk2 mutations and microbial pathogens.

methodsPBMCs from LRRK2-PD, GBA-PD, and iPD patients plus age- and sex-matched controls were treated ex vivo with live P. aeruginosa and pharmacological agents that block LRRK2 kinase activity (MLi-2) or enhance glucocerebrosidase (GCase) activation (NCGC00188758) to measure enzymatic activities and cytokine release.

resultsGBA-PD PBMCs exhibited increased P. aeruginosa-dependent secretion of specific inflammatory cytokines including interleukin-1β. Antigen presentation was increased in LRRK2-PD nonclassical monocytes treated with the GCase activator. Levels of pRab10, a proxy for LRRK2 kinase activity, were increased in GBA-PD classical monocytes relative to NHC and iPD. GCase activator treatment increased pRab10 expression in LRRK2-PD intermediate monocytes. GBA-PD and individual treatments with MLi-2 or GCase activator were associated with reduced P. aeruginosa-dependent LRRK2 protein levels in PBMC subsets.

conclusionsThis work demonstrates that PD-linked mutations in LRRK2 and GBA1 converge on peripheral blood immune cell dysregulation, as evinced by the ability of LRRK2 inhibitors and GCase activators to modulate the ex vivo immune response to bacterial exposure. © 2025 The Author(s). Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.

Indexed as

GlucosylceramidaseLeucine-Rich Repeat Serine-Threonine Protein Kinase-2Leukocytes, MononuclearParkinson DiseasePseudomonas aeruginosaAgedFemaleHumansMaleMiddle AgedMutationGBA protein, humanGlucosylceramidaseLeucine-Rich Repeat Serine-Threonine Protein Kinase-2LRRK2 protein, humanGBA1glucocerebrosidaseinflammationLRRK2Parkinson's Disease

Identifiers

PMID41257354
PMCPMC13022586

What OpenQuestion holds

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LicenceCC BY
Read underepoch 390

Registered trials

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.