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The Neuroinflammatory Acute Phase Response in Parkinsonian-Related Disorders

Ayton, Scott ; Hall, Sara LU ; Janelidze, Shorena LU ; Kalinowski, Pawel ; Palmqvist, Sebastian LU orcid ; Belaidi, Abdel A. ; Roberts, Blaine ; Roberts, Anne ; Stomrud, Erik LU orcid and Bush, Ashley I. , et al. (2022) In Movement Disorders 37(5). p.993-1003
Abstract

Background: Neuroinflammation is implicated in the pathophysiology of Parkinson's disease (PD) and related conditions, yet prior clinical biomarker data report mixed findings. Objectives: The aim was to measure a panel of neuroinflammatory acute phase response (APR) proteins in the cerebrospinal fluid (CSF) of participants with PD and related disorders. Methods: Eleven APR proteins were measured in the CSF of 867 participants from the BioFINDER cohort who were healthy (612) or had a diagnosis of PD (155), multiple system atrophy (MSA) (26), progressive supranuclear palsy (PSP) (22), dementia with Lewy bodies (DLB) (23), or Parkinson’s disease with dementia (PDD) (29). Results: CSF APR proteins were mostly unchanged in PD, with only... (More)

Background: Neuroinflammation is implicated in the pathophysiology of Parkinson's disease (PD) and related conditions, yet prior clinical biomarker data report mixed findings. Objectives: The aim was to measure a panel of neuroinflammatory acute phase response (APR) proteins in the cerebrospinal fluid (CSF) of participants with PD and related disorders. Methods: Eleven APR proteins were measured in the CSF of 867 participants from the BioFINDER cohort who were healthy (612) or had a diagnosis of PD (155), multiple system atrophy (MSA) (26), progressive supranuclear palsy (PSP) (22), dementia with Lewy bodies (DLB) (23), or Parkinson’s disease with dementia (PDD) (29). Results: CSF APR proteins were mostly unchanged in PD, with only haptoglobin and α1-antitrypsin significantly elevated compared to controls. These proteins were variably increased in the other disorders. Certain protein components yielded unique signatures according to diagnosis: ferritin and transthyretin were selectively elevated in MSA and discriminated these patients from all others. Haptoglobin was selectively increased in PSP, discriminating this disease from MSA when used in combination with ferritin and transthyretin. This panel of proteins did not correlate well with severity of motor impairment in any disease category, but several (particularly ceruloplasmin and ferritin) were associated with memory performance (Mini-Mental State Examination) in patients with DLB and PDD. Conclusions: These findings provide new insights into inflammatory changes in PD and related disorders while also introducing biomarkers of potential clinical diagnostic utility.

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organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
Lewy Body Dementia, multiple system atrophy, neuroinflammation, Parkinson's disease, progressive supranuclear palsy
in
Movement Disorders
volume
37
issue
5
pages
993 - 1003
publisher
John Wiley & Sons Inc.
external identifiers
  • scopus:85124545662
  • pmid:35137973
ISSN
0885-3185
DOI
10.1002/mds.28958
language
English
LU publication?
yes
id
7bb1a8ad-812c-4fc1-b632-9f7fe45bfb44
date added to LUP
2022-04-13 12:23:38
date last changed
2024-06-18 15:42:01
@article{7bb1a8ad-812c-4fc1-b632-9f7fe45bfb44,
  abstract     = {{<p>Background: Neuroinflammation is implicated in the pathophysiology of Parkinson's disease (PD) and related conditions, yet prior clinical biomarker data report mixed findings. Objectives: The aim was to measure a panel of neuroinflammatory acute phase response (APR) proteins in the cerebrospinal fluid (CSF) of participants with PD and related disorders. Methods: Eleven APR proteins were measured in the CSF of 867 participants from the BioFINDER cohort who were healthy (612) or had a diagnosis of PD (155), multiple system atrophy (MSA) (26), progressive supranuclear palsy (PSP) (22), dementia with Lewy bodies (DLB) (23), or Parkinson’s disease with dementia (PDD) (29). Results: CSF APR proteins were mostly unchanged in PD, with only haptoglobin and α1-antitrypsin significantly elevated compared to controls. These proteins were variably increased in the other disorders. Certain protein components yielded unique signatures according to diagnosis: ferritin and transthyretin were selectively elevated in MSA and discriminated these patients from all others. Haptoglobin was selectively increased in PSP, discriminating this disease from MSA when used in combination with ferritin and transthyretin. This panel of proteins did not correlate well with severity of motor impairment in any disease category, but several (particularly ceruloplasmin and ferritin) were associated with memory performance (Mini-Mental State Examination) in patients with DLB and PDD. Conclusions: These findings provide new insights into inflammatory changes in PD and related disorders while also introducing biomarkers of potential clinical diagnostic utility.</p>}},
  author       = {{Ayton, Scott and Hall, Sara and Janelidze, Shorena and Kalinowski, Pawel and Palmqvist, Sebastian and Belaidi, Abdel A. and Roberts, Blaine and Roberts, Anne and Stomrud, Erik and Bush, Ashley I. and Hansson, Oskar}},
  issn         = {{0885-3185}},
  keywords     = {{Lewy Body Dementia; multiple system atrophy; neuroinflammation; Parkinson's disease; progressive supranuclear palsy}},
  language     = {{eng}},
  number       = {{5}},
  pages        = {{993--1003}},
  publisher    = {{John Wiley & Sons Inc.}},
  series       = {{Movement Disorders}},
  title        = {{The Neuroinflammatory Acute Phase Response in Parkinsonian-Related Disorders}},
  url          = {{http://dx.doi.org/10.1002/mds.28958}},
  doi          = {{10.1002/mds.28958}},
  volume       = {{37}},
  year         = {{2022}},
}