Growing Evidence for the Role of the Immune System in Parkinson’s Disease

1 December 2022

Experts review the latest research evidence for the link between immune activation and neuroinflammation and Parkinson’s disease in this supplement to the Journal of Parkinson’s Disease

Amsterdam, NL – In this special supplement to the Journal of Parkinson’s Disease, “The Immune System in Parkinson’s Disease,” experts highlight the latest research breakthroughs on the links between immune activation and neuroinflammation and Parkinson’s disease (PD) and discuss the challenges and novel therapeutic strategies targeting the immune system with the hope of reducing or reversing neurodegeneration.

Although multiple independent studies have provided evidence of the involvement of central and peripheral immune and inflammatory processes in PD, the cause-and-effect relationship between neuroinflammation and neurodegeneration in PD is difficult to determine as the initiating event(s) likely occur many years before neuronal loss and clinical manifestations arise. There is growing evidence, however, that inflammation might play a causative role in PD rather than being a consequence or an epiphenomenon of the neurodegenerative process.

“PD risk is influenced by many factors including a mix of immunogenetics and the environment, such as infection history,” commented Guest Editors Bastiaan R. Bloem, MD, PhD, Patrik Brundin, MD, PhD, Ashley Harms, PhD, Cecilia Lindestam Arlehamn, PhD, Eng King Tan, MD, and Caroline Williams-Gray, PhD. “In recent years, increasing evidence suggests an association with autoimmune conditions and involvement of the immune system or its aberrant responses in patients with PD and various experimental models.”

Topics included in this supplement cover:

• Immunogenetic determinants of PD
• Epidemiological evidence for an immune component of PD
• Influence of infections and the microbiome
• Links between the GBA1 gene and immune changes in PD
• The role of T lymphocytes
• The role of B lymphocytes
• Natural killer cells in PD
• Age-related immune changes in PD
• Microglial activation in the brains of patients with neurodegenerative disorders including PD
• Current evidence and knowledge gaps around inflammasome activation in PD
• The role of central and peripheral inflammation
• Neuroinflammation and immune changes in prodromal PD
• Inflammatory animal models of PD
• Biomarkers of inflammation in PD
• Therapeutic strategies targeting the immune system in PD

Patients with PD and other synucleinopathies often exhibit autoimmune features, including immune cells (CD4+ and CD8+ T lymphocytes) that recognize forms of alpha-synuclein. A review article by Benjamin D. Hobson, MD/PhD student, and David Sulzer, PhD, both of Columbia University Irving Medical Center, focuses on how peripheral T lymphocytes can enter into brain areas that are primarily affected in PD. Neurons in these brain regions can present antigens bound to MHC class 1 molecules on the cell surface and signal the cell’s physiological state to immune cells (such as T cells). Certain subtypes of T cells (CD8+) have been shown to bind to the antigen: MHC class 1 complex on the cell surface promoting further immune responses leading to cell damage and finally death of the neurons.

Caption: Possible roles of neuronal antigen presentation in Parkinson’s disease. Schematic depicting potential stimuli leading to MHC-I upregulation and antigen presentation in dopamine neurons and possible downstream consequences. TCR, T cell receptor; DA, dopamine; Ags, antigens. Credit: B.D. Hobson and D. Sulzer, Journal of Parkinson’s Disease.

“Recent animal models suggest the possibility of T cell autoreactivity to mitochondrial antigens in PD,” noted Dr. Sulzer. “However, it remains unclear if neuronal antigen presentation plays a role in PD or other neurodegenerative disorders, and efforts are underway to better understand the potential impact of autoimmune responses on neurodegeneration.”

“In summary, multiple independent studies in clinical and preclinical models have provided corroborative evidence of the involvement of central and peripheral immune and inflammatory processes in PD,” noted the Guest Editors. “Our knowledge of how the immune system contributes to PD pathogenesis is constantly evolving, with increasing evidence for a role of several genes and susceptibility loci.”

A major challenge is to use these data and knowledge to identify specific targets within the immune system or target major pathogenic proteins involved in aberrant immune responses; and potentially to identify subsets of patients who are more likely to respond to immune modulatory therapies.

“Clinical trials targeting alpha-synuclein have already commenced and both clinical and experimental trials focusing on different immune components are ongoing,” commented co-Guest Editor and JPD’s co-Editor-in-Chief Bastiaan R. Bloem, MD, PhD, Center of Expertise for Parkinson & Movement Disorders, Radboud University Medical Centre, Nijmegen.

The Guest Editors emphasize that considerable research is still needed to determine the individual and collective roles of the individual immune cells (and their subsets), and how they interact with each other within the neurovascular units and with alpha-synuclein and other key proteins.

“Longitudinal studies using molecular imaging that measures microglial activation in the brain, and detailed blood and CSF immune function tests and phenotyping in at-risk subjects or prodromic PD may identify crucial clues on the temporal cause-effect relationship between neuroinflammation and PD,” Professor Bloem concluded.

Parkinson’s disease is a slowly progressive disorder that affects movement, muscle control, and balance. It is the second most common age-related neurodegenerative disorder affecting about 3% of the population by the age of 65 and up to 5% of individuals over 85 years of age.

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Supplement: The Immune System in Parkinson’s Disease
Guest Editors: Bastiaan R. Bloem, MD, PhD, Patrik Brundin, MD, PhD, Ashley Harms, PhD, Cecilia Lindestam Arlehamn, PhD, Eng King Tan, MD, and Caroline Williams-Gray, PhD
Journal of Parkinson’s Disease Volume 12, Supplement 1
Openly available at

Featured Article
“Neuronal Presentation of Antigen and Its Possible Role in Parkinson’s Disease,” by Benjamin D. Hobson, MD/PhD student, and David Sulzer, PhD ( Openly available at

For additional information contact Diana Murray, IOS Press, at +1 718-640-5678 or Journalists wishing to interview the Guest Editors or contributing authors should contact Bastiaan R. Bloem, MD, PhD, at, Eng King Tan, MD, at, or Caroline Williams-Gray, PhD, at

About the Journal of Parkinson's Disease
Now in its 12th volume, the Journal of Parkinson’s Disease (JPD) is dedicated to providing an open forum for original research in basic science, translational research and clinical medicine that will expedite our fundamental understanding and improve treatment of Parkinson’s disease. The journal is international and multidisciplinary and aims to promote progress in the epidemiology, etiology, genetics, molecular correlates, pathogenesis, pharmacology, psychology, diagnosis, and treatment of Parkinson’s disease. It publishes research reports, reviews, short communications, and letters-to-the-editor and offers very rapid publication and an affordable open access option. JPD has a 2021 Journal Impact Factor of 5.520 according to Journal Citation Reports (Clarivate, 2022) and is published by IOS Press.

About IOS Press
IOS Press is an independent international scientific, technical, medical (STM) publishing house established in 1987 in Amsterdam. We produce around 90 journals and 70 books annually in a broad range of subject categories, primarily specializing in health and life sciences (including neurosciences, medical informatics, cancer research, and rehabilitation) and computer sciences (including artificial intelligence, data science, and semantic web). In addition, we offer specialized services that support scientific advancement.