Inflammation may change the course of Parkinson’s disease

Inflammation may start early in Parkinson's disease (PD), long before motor symptoms occur, according to Prof. Vidar Gundersen (University of Oslo, Norway) in a plenary talk about the central theme of EAN 2019: “Neuroinflammation” [1].

In PD, microglia are activated and are present in dopamine neurons long before the accumulation of α-synuclein pathology. This implies that microglial activation probably contributes to the development of α-synuclein pathology [2]. Early activation of microglia has also been demonstrated in translocator protein (TSPO) PET imaging [3]. Both pro- and anti-inflammatory cytokines are activated, such as TNF and IL-1-beta. The pro-inflammatory cytokine IFN-gamma is also involved in inflammatory-induced neurodegeneration in PD [4].

Prof. Gundersen went on to explain how inflammation may contribute to dopamine neurodegeneration. He suggested that the adaptive immune system is involved in PD pathology and that PD might even be an auto-immune disease. When in the disease process naïve T cells prime is unclear. “If microglia are activated and present α-synuclein to T cells prior to neuronal death”, he postulated, “then MS drugs might be effective against PD”.

Prof. Gundersen also touched upon the gut hypothesis. In this 'gut to brain' scenario, PD pathology may start in the gastrointestinal tract and then spread through the vagus nerve to the brain. α-Synuclein has been found to be located in gut neurons before the start of motor symptoms in PD, not in controls [5]. However, other observations contradict this concept. “The only way to find out is a proper interventional study”, said Prof. Gundersen. An attempt was recently made in a placebo-controlled trial of the glucagon-like peptide-1 (GLP-1) receptor agonist exenatide [6]. This intervention had positive effects on off-medication motor scores in PD, which were sustained beyond the exposure period. However, whether exenatide affects the underlying disease pathophysiology or only induces long-lasting symptomatic effects, is uncertain. Prof. Gundersen said larger, longer-duration studies are needed which include patients with prodromal PD. His overall conclusion was: “Inflammation matters: it may change the course of PD”.

1. 
   
   1. Gundersen V. EAN 2019, PLEN03_2.
   2. Olanow CW, et al. Brain. 2019;142(6):1690-1700.
   3. Iannacone S, et al. Parkinsonism Relat Disord. 2013;19(1):47-52.
   4. Mangano EN, et al. Neurobiol Aging. 2012;33(7):1411-26.
   5. Shannon KM, et al. Mov Disord. 2012;27(6):709-15.
   6. Athauda D, et al. Lancet. 2017;390(10103):1664-75.

 



Posted on 27 September, 201916 February, 2024