Neuroinflammation and Immune Changes in Prodromal Parkinson’s Disease and Other Synucleinopathies

TY - JOUR

T1 - Neuroinflammation and Immune Changes in Prodromal Parkinson’s Disease and Other Synucleinopathies

AU - Terkelsen, Miriam Højholt

AU - Klæstrup, Ida Hyllen

AU - Hvingelby, Victor

AU - Lauritsen, Johanne

AU - Pavese, Nicola

AU - Romero-Ramos, Marina

PY - 2022/9

Y1 - 2022/9

N2 - Multiple lines of clinical and pre-clinical research support a pathogenic role for neuroinflammation and peripheral immune system dysfunction in Parkinson's disease. In this paper, we have reviewed and summarised the published literature reporting evidence of neuroinflammation and peripheral immune changes in cohorts of patients with isolated REM sleep behaviour disorder and non-manifesting carriers of GBA or LRRK2 gene mutations, who have increased risk for Parkinsonism and synucleinopathies, and could be in the prodromal stage of these conditions. Taken together, the findings of these studies suggest that the early stages of pathology in Parkinsonism involve activation of both the central and peripheral immune systems with significant crosstalk. We consider these findings with respect to those found in patients with clinical Parkinson's disease and discuss their possible pathological roles. Moreover, those factors possibly associated with the immune response, such as the immunomodulatory role of the affected neurotransmitters and the changes in the gut-brain axis, are also considered.

AB - Multiple lines of clinical and pre-clinical research support a pathogenic role for neuroinflammation and peripheral immune system dysfunction in Parkinson's disease. In this paper, we have reviewed and summarised the published literature reporting evidence of neuroinflammation and peripheral immune changes in cohorts of patients with isolated REM sleep behaviour disorder and non-manifesting carriers of GBA or LRRK2 gene mutations, who have increased risk for Parkinsonism and synucleinopathies, and could be in the prodromal stage of these conditions. Taken together, the findings of these studies suggest that the early stages of pathology in Parkinsonism involve activation of both the central and peripheral immune systems with significant crosstalk. We consider these findings with respect to those found in patients with clinical Parkinson's disease and discuss their possible pathological roles. Moreover, those factors possibly associated with the immune response, such as the immunomodulatory role of the affected neurotransmitters and the changes in the gut-brain axis, are also considered.

KW - GBA

KW - LRRK2

KW - Microglia

KW - Parkinson’s disease

KW - T-cells

KW - alpha-synuclein

KW - monocytes

KW - prodromal

KW - Neuroinflammatory Diseases

KW - Humans

KW - Synucleinopathies

KW - Prodromal Symptoms

KW - Parkinson Disease/complications

KW - REM Sleep Behavior Disorder/complications

KW - alpha-Synuclein

U2 - 10.3233/JPD-223245

DO - 10.3233/JPD-223245

M3 - Review

C2 - 35723115

SN - 1877-7171

VL - 12

SP - S149-S163

JO - Journal of Parkinson's Disease

JF - Journal of Parkinson's Disease

IS - s1

ER -