Border-associated macrophages mediate the neuroinflammatory response in an alpha-synuclein model of Parkinson disease

Neuroinflammation and accumulation of alpha-synuclein (a-syn) are core features of Parkinson disease (PD). We found that a-syn-induced neuroinflammation is driven by antigen presentation from CNS resident macrophages. A subset of these, border-associated macrophages (BAMs), expand and express genes and proteins necessary for immune cell recruitment, infiltration, and antigen presentation, whereas depletion of BAMs prevents neuroinflammation and neurodegeneration. These results point to a critical role for BAMs in initiating PD pathogenesis. Overall design: Mononuclear cells from 3-4 ventral midbrains pooled per sample, and sorted for CD45+ CD11b+ CX3CR1+ Ly6C- Ly6G- 301 and NK1.1- 302 cells on a BD FACsAria. Sorted cells were loaded onto the 10X Chromium 303 platform (10X genomics), and libraries were constructed using the Single Cell 3' 304 Reagent Kit V2 according to the manufacturer's instructions. Two biological replicates for each group were processed separately.