Blood and Cerebrospinal Fluid Biomarkers of Inflammation in Parkinson’s Disease

Abstract

Given the clear role of inflammation in the pathogenesis of Parkinson’s disease (PD) and its impact on incidence and phenotypical characteristics, this review provides an overview with focus on inflammatory biofluid markers in blood and cerebrospinal fluid (CSF) in PD patient cohorts. In preparation for clinical trials targeting the immune system, we specifically address the following questions: 1) What evidence do we have for pro-inflammatory profiles in blood and in CSF of sporadic and genetic PD patients? 2) Is there a role of anti-inflammatory mediators in blood/CSF? 3) Do inflammatory profiles in blood reflect those in CSF indicative of a cross-talk between periphery and brain? 4) Do blood/CSF inflammatory profiles change over the disease course as assessed in repeatedly taken biosamples? 5) Are blood/CSF inflammatory profiles associated with phenotypical trajectories in PD? 6) Are blood/CSF inflammatory profiles associated with CSF levels of neurodegenerative/PD-specific biomarkers? Knowledge on these questions will inform future strategies for patient stratification and cohort enrichment as well as suitable outcome measures for clinical trials.

Brain and systemic inflammation in de novo Parkinson’s disease

“…Previous studies of chemokine and cytokine levels in plasma or CSF have pointed to elevations in several pro-inflammatory molecules, although studies vary in the degree and particular cytokines or chemokines observed [13][14][15][16][17][18][19][20][21][22][23][24][25][26] . In the blood, the most consistent changes have been noted in IL-1β and some studies have also pointed to changes in IL-2, IFN-γ, and TNF-α 26 . Two recent studies have evaluated serum cytokines in early-stage PD subjects 13 25 .…”

“…Peptides derived from alpha-synuclein (αsyn), the key protein that aggregates in PD and the primary component of Lewy Bodies, can activate T-cells from PD patients 12 . Pro-inflammatory cytokines and chemokines are elevated in blood and cerebrospinal fluid (CSF) specimens from subjects with PD [13][14][15][16][17][18][19][20][21][22][23][24][25][26] . Brain imaging techniques using ligands against translocator protein 18kd (TSPO) as a marker for neuroinflammation have pointed to increased TSPO signal in PD patients [27][28][29][30][31][32] .…”

Linking Immune Activation and Parkinson’s Disease

“…PD is influenced by many factors including a mix of immunogenetics and the environment, such as infection history. In recent years, increasing evidence suggests an association with autoimmune conditions, with the involvement of the immune system or its aberrant responses in patients and various experimental models [1][2][3][4][5][6][7][8][9][10][11][12][13][14][15][16][17][18][19]. In this special issue, our authors highlight the latest research breakthroughs on the links between immune activation and neuroinflammation and PD, and discuss the challenges and novel therapeutic strategies targeting the immune system ISSN 1877-7171/$35.00 © 2022 -IOS Press.…”

“…T cells, neutrophils, monocytes, dendritic cells, and natural killer (NK) cells form the cellular immunity, while humoral immunity involves antibodies and complement proteins. Several clinical studies using blood and cerebrospinal fluid (CSF) from PD patients have suggested involvement of both cellular and humoral immunity with evidence of changes in pro-inflammatory and anti-inflammatory mediators [5]. B lymphocytes (especially regulatory subset) are decreased in PD though the relative temporal changes in peripheral and CSF B cells over time in patients still need to be further evaluated [6].…”

“…In summary, multiple independent studies in clinical and pre-clinical models have provided corroborative evidence of the involvement of central and peripheral immune and inflammatory processes in PD [1][2][3][4][5][6][7][8][9][10][11][12][13][14][15][16][17][18][19]. 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 [1,2].…”