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T cell responses towards PINK1 and α-synuclein are elevated in prodromal Parkinson’s disease

Johansson, Emil LU orcid ; Freuchet, Antoine ; Williams, Gregory P. ; Michealis, Tanner ; Frazier, April ; Litvan, Irene ; Goldman, Jennifer G. ; Alcalay, Roy N. ; Standaert, David G. and Amara, Amy W. , et al. (2025) In npj Parkinson's Disease 11(1).
Abstract

A role of the immune system in Parkinson’s disease (PD) progression has long been suspected due to the increased frequency of activated glial cells and infiltrating T cells in the substantia nigra. It was previously reported that PD donors have increased T cell responses towards PINK1 and α-synuclein (α-syn), two Lewy body-associated proteins. Further, T cell reactivity towards α-syn was highest closer to disease onset, highlighting that autoreactive T cells might play a role in PD pathogenesis. However, whether T cell autoreactivity is present during prodromal PD is unknown. Here, we investigated T cell responses towards PINK1 and α-syn in donors at high risk of developing PD (i.e. prodromal PD: genetic risk, hyposmia, and or REM sleep... (More)

A role of the immune system in Parkinson’s disease (PD) progression has long been suspected due to the increased frequency of activated glial cells and infiltrating T cells in the substantia nigra. It was previously reported that PD donors have increased T cell responses towards PINK1 and α-synuclein (α-syn), two Lewy body-associated proteins. Further, T cell reactivity towards α-syn was highest closer to disease onset, highlighting that autoreactive T cells might play a role in PD pathogenesis. However, whether T cell autoreactivity is present during prodromal PD is unknown. Here, we investigated T cell responses towards PINK1 and α-syn in donors at high risk of developing PD (i.e. prodromal PD: genetic risk, hyposmia, and or REM sleep behavior disorder), in comparison to PD and healthy control donors. T cell reactivity to these two autoantigens was detected in prodromal PD at levels comparable to those detected in individuals with clinically diagnosed PD. Aligned with the increased incidence of PD in males, we found that males with PD, but not females, had elevated T cell reactivity compared to healthy controls. However, among prodromal PD donors, males and females had elevated T cell responses. These differing trends in reactivity highlights the need for further studies of the impact of biological sex on neuroinflammation and PD progression.

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organization
publishing date
type
Contribution to journal
publication status
published
subject
in
npj Parkinson's Disease
volume
11
issue
1
article number
137
publisher
Springer Nature
external identifiers
  • pmid:40419563
  • scopus:105006419078
ISSN
2373-8057
DOI
10.1038/s41531-025-01001-3
language
English
LU publication?
yes
id
597ecda8-77aa-45e0-9282-0e5f4d46e637
date added to LUP
2025-07-11 10:35:56
date last changed
2025-07-12 03:00:02
@article{597ecda8-77aa-45e0-9282-0e5f4d46e637,
  abstract     = {{<p>A role of the immune system in Parkinson’s disease (PD) progression has long been suspected due to the increased frequency of activated glial cells and infiltrating T cells in the substantia nigra. It was previously reported that PD donors have increased T cell responses towards PINK1 and α-synuclein (α-syn), two Lewy body-associated proteins. Further, T cell reactivity towards α-syn was highest closer to disease onset, highlighting that autoreactive T cells might play a role in PD pathogenesis. However, whether T cell autoreactivity is present during prodromal PD is unknown. Here, we investigated T cell responses towards PINK1 and α-syn in donors at high risk of developing PD (i.e. prodromal PD: genetic risk, hyposmia, and or REM sleep behavior disorder), in comparison to PD and healthy control donors. T cell reactivity to these two autoantigens was detected in prodromal PD at levels comparable to those detected in individuals with clinically diagnosed PD. Aligned with the increased incidence of PD in males, we found that males with PD, but not females, had elevated T cell reactivity compared to healthy controls. However, among prodromal PD donors, males and females had elevated T cell responses. These differing trends in reactivity highlights the need for further studies of the impact of biological sex on neuroinflammation and PD progression.</p>}},
  author       = {{Johansson, Emil and Freuchet, Antoine and Williams, Gregory P. and Michealis, Tanner and Frazier, April and Litvan, Irene and Goldman, Jennifer G. and Alcalay, Roy N. and Standaert, David G. and Amara, Amy W. and Stover, Natividad and Fon, Edward A. and Postuma, Ronald B. and Sidney, John and Sulzer, David and Lindestam Arlehamn, Cecilia S. and Sette, Alessandro}},
  issn         = {{2373-8057}},
  language     = {{eng}},
  number       = {{1}},
  publisher    = {{Springer Nature}},
  series       = {{npj Parkinson's Disease}},
  title        = {{T cell responses towards PINK1 and α-synuclein are elevated in prodromal Parkinson’s disease}},
  url          = {{http://dx.doi.org/10.1038/s41531-025-01001-3}},
  doi          = {{10.1038/s41531-025-01001-3}},
  volume       = {{11}},
  year         = {{2025}},
}