npj Parkinson's Disease (Dec 2023)

Sex-dimorphic neuroprotective effect of CD163 in an α-synuclein mouse model of Parkinson’s disease

  • Sara A. Ferreira,
  • Conghui Li,
  • Ida H. Klæstrup,
  • Zagorka Vitic,
  • Rikke K. Rasmussen,
  • Asger Kirkegaard,
  • Gitte U. Toft,
  • Cristine Betzer,
  • Pia Svendsen,
  • Poul H. Jensen,
  • Yonglun Luo,
  • Anders Etzerodt,
  • Søren K. Moestrup,
  • Marina Romero-Ramos

DOI
https://doi.org/10.1038/s41531-023-00606-w
Journal volume & issue
Vol. 9, no. 1
pp. 1 – 21

Abstract

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Abstract Alpha-synuclein (α-syn) aggregation and immune activation represent hallmark pathological events in Parkinson’s disease (PD). The PD-associated immune response encompasses both brain and peripheral immune cells, although little is known about the immune proteins relevant for such a response. We propose that the upregulation of CD163 observed in blood monocytes and in the responsive microglia in PD patients is a protective mechanism in the disease. To investigate this, we used the PD model based on intrastriatal injections of murine α-syn pre-formed fibrils in CD163 knockout (KO) mice and wild-type littermates. CD163KO females revealed an impaired and differential early immune response to α-syn pathology as revealed by immunohistochemical and transcriptomic analysis. After 6 months, CD163KO females showed an exacerbated immune response and α-syn pathology, which ultimately led to dopaminergic neurodegeneration of greater magnitude. These findings support a sex-dimorphic neuroprotective role for CD163 during α-syn-induced neurodegeneration.