Skip to main content

Lund University Publications

LUND UNIVERSITY LIBRARIES

CSF markers of neuroinflammation, synaptic dysfunction and [18F]DOPA-PET in Parkinson's disease

Hauer, Kevin Oliveira LU ; Hall, Sara LU ; Nahimi, Adjmal LU ; Strandberg, Olof LU ; Ohlsson, Tomas ; Jögi, Jonas LU orcid ; Stomrud, Erik LU orcid ; Janelidze, Shorena LU ; Hansson, Oskar LU orcid and Smith, Ruben LU (2025) In Parkinsonism and Related Disorders 139.
Abstract

Introduction: Neuromelanin containing cell loss, neuroinflammation and synaptic dysfunction are believed to contribute to Parkinson's disease (PD) pathogenesis. [18F]DOPA PET reflects dopamine storage capacity in the putamen, while midbrain off-target retention of [18F]RO948 is hypothesized to reflect neuromelanin. Objectives: To investigate associations between disease duration, cerebrospinal fluid (CSF) markers of neurodegeneration, synaptic dysfunction, neuroinflammation, and dopamine synaptic loss as measured by [18F]DOPA PET in PD patients. We further aimed to explore whether reduced midbrain retention of [18F]RO948 relates to [18F]DOPA PET and CSF markers. Methods:... (More)

Introduction: Neuromelanin containing cell loss, neuroinflammation and synaptic dysfunction are believed to contribute to Parkinson's disease (PD) pathogenesis. [18F]DOPA PET reflects dopamine storage capacity in the putamen, while midbrain off-target retention of [18F]RO948 is hypothesized to reflect neuromelanin. Objectives: To investigate associations between disease duration, cerebrospinal fluid (CSF) markers of neurodegeneration, synaptic dysfunction, neuroinflammation, and dopamine synaptic loss as measured by [18F]DOPA PET in PD patients. We further aimed to explore whether reduced midbrain retention of [18F]RO948 relates to [18F]DOPA PET and CSF markers. Methods: Participants were part of the BioFINDER studies. CSF biomarkers were analyzed for controls (n = 623), PD participants (n = 226) and Dementia with Lewy bodies (DLB; n = 33). [18F]RO948 PET was performed in controls (n = 514), PD (n = 77) and DLB (n = 47) and [18F]DOPA PET in PD (n = 58) and DLB (n = 22). Results: PD patients showed higher CSF neurofilament light (NfL) levels (pg/ml [mean ± SD] 159 ± 139) vs. controls (137 ± 90, p < 0.001), and lower neurogranin (pg/ml [mean ± SD] 620 ± 255) vs (772 ± 283, p < 0.001). Lower [18F]DOPA uptake correlated with longer disease duration (ρ = −0.46, p < 0.001), higher NfL (ρ = −0.39, p = 0.03), lower neurogranin (ρ = 0.50, p = 0.003) and NPTX2 levels (ρ = 0.36, p = 0.049). We found no associations between neuroinflammatory markers and [18F]DOPA PET. Substantia nigra [18F]RO948 signal was lower in PD ([mean ± SD] 1.67 ± 0.22) vs controls (1.76 ± 0.3, p < 0.001) but did not correlate with disease duration, CSF markers or [18F]DOPA-PET. Conclusions: In PD patients, a decrease in [18F]DOPA PET retention correlated with disease duration as well as CSF neurodegenerative and synaptic biomarkers but not with inflammatory biomarkers or [18F]RO948 PET midbrain off-target retention.

(Less)
Please use this url to cite or link to this publication:
author
; ; ; ; ; ; ; ; and
organization
publishing date
type
Contribution to journal
publication status
published
subject
in
Parkinsonism and Related Disorders
volume
139
article number
108005
publisher
Elsevier
external identifiers
  • scopus:105014366367
  • pmid:40885039
ISSN
1353-8020
DOI
10.1016/j.parkreldis.2025.108005
language
English
LU publication?
yes
id
c43d59ed-3791-4a84-bab9-f18ce3a5811a
date added to LUP
2025-10-10 15:15:19
date last changed
2025-10-11 03:16:27
@article{c43d59ed-3791-4a84-bab9-f18ce3a5811a,
  abstract     = {{<p>Introduction: Neuromelanin containing cell loss, neuroinflammation and synaptic dysfunction are believed to contribute to Parkinson's disease (PD) pathogenesis. [<sup>18</sup>F]DOPA PET reflects dopamine storage capacity in the putamen, while midbrain off-target retention of [<sup>18</sup>F]RO948 is hypothesized to reflect neuromelanin. Objectives: To investigate associations between disease duration, cerebrospinal fluid (CSF) markers of neurodegeneration, synaptic dysfunction, neuroinflammation, and dopamine synaptic loss as measured by [<sup>18</sup>F]DOPA PET in PD patients. We further aimed to explore whether reduced midbrain retention of [<sup>18</sup>F]RO948 relates to [<sup>18</sup>F]DOPA PET and CSF markers. Methods: Participants were part of the BioFINDER studies. CSF biomarkers were analyzed for controls (n = 623), PD participants (n = 226) and Dementia with Lewy bodies (DLB; n = 33). [<sup>18</sup>F]RO948 PET was performed in controls (n = 514), PD (n = 77) and DLB (n = 47) and [<sup>18</sup>F]DOPA PET in PD (n = 58) and DLB (n = 22). Results: PD patients showed higher CSF neurofilament light (NfL) levels (pg/ml [mean ± SD] 159 ± 139) vs. controls (137 ± 90, p &lt; 0.001), and lower neurogranin (pg/ml [mean ± SD] 620 ± 255) vs (772 ± 283, p &lt; 0.001). Lower [<sup>18</sup>F]DOPA uptake correlated with longer disease duration (ρ = −0.46, p &lt; 0.001), higher NfL (ρ = −0.39, p = 0.03), lower neurogranin (ρ = 0.50, p = 0.003) and NPTX2 levels (ρ = 0.36, p = 0.049). We found no associations between neuroinflammatory markers and [<sup>18</sup>F]DOPA PET. Substantia nigra [<sup>18</sup>F]RO948 signal was lower in PD ([mean ± SD] 1.67 ± 0.22) vs controls (1.76 ± 0.3, p &lt; 0.001) but did not correlate with disease duration, CSF markers or [<sup>18</sup>F]DOPA-PET. Conclusions: In PD patients, a decrease in [<sup>18</sup>F]DOPA PET retention correlated with disease duration as well as CSF neurodegenerative and synaptic biomarkers but not with inflammatory biomarkers or [<sup>18</sup>F]RO948 PET midbrain off-target retention.</p>}},
  author       = {{Hauer, Kevin Oliveira and Hall, Sara and Nahimi, Adjmal and Strandberg, Olof and Ohlsson, Tomas and Jögi, Jonas and Stomrud, Erik and Janelidze, Shorena and Hansson, Oskar and Smith, Ruben}},
  issn         = {{1353-8020}},
  language     = {{eng}},
  publisher    = {{Elsevier}},
  series       = {{Parkinsonism and Related Disorders}},
  title        = {{CSF markers of neuroinflammation, synaptic dysfunction and [<sup>18</sup>F]DOPA-PET in Parkinson's disease}},
  url          = {{http://dx.doi.org/10.1016/j.parkreldis.2025.108005}},
  doi          = {{10.1016/j.parkreldis.2025.108005}},
  volume       = {{139}},
  year         = {{2025}},
}