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

Alpha-synuclein (alpha-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 alpha-syn pre-formed fibrils in CD163 knockout (KO) mice and wild-type littermates. CD163KO females revealed an impaired and differential early immune response to alpha-syn pathology as revealed by immunohistochemical and transcriptomic analysis. After 6 months, CD163KO females showed an exacerbated immune response and alpha-syn pathology, which ultimately led to dopaminergic neurodegeneration of greater magnitude. These findings support a sex-dimorphic neuroprotective role for CD163 during alpha-syn-induced neurodegeneration.

Automated summary

Alpha-synuclein aggregation and immune activation are hallmark events in Parkinson's disease. CD163 upregulation in blood monocytes and microglia may represent a protective mechanism in PD.