Figure 2.

Dynamics and functions of microglia in chronic neurodegenerative diseases. (A) In the normal brain, the microglial population has a surveillant phenotype, maintaining homeostasis. The microglia population is maintained by self-renewal, while the perivascular macrophages can be renewed by bone-marrow-derived progenitors. In Alzheimer’s disease (AD) microglia proliferate and accumulate around plaques of amyloid β (Aβ), participating in the attempted removal of the misfolded protein. Perivascular macrophages have a more efficient phagocytic activity than microglial cells in AD. In AD, the microglial population is increased without a contribution from bone-marrow-derived cells. Microglia are expanded and activated during the course of amyotrophic lateral sclerosis (ALS), without a contribution from circulating progenitors. In prion disease, the microglial population is expanded dramatically by local proliferation (B; BrdU⁺), being primed to give an exaggerated response to systemic inflammatory events. Little evidence is available about the expansion/renewal of the microglial population during Parkinson’s or Huntington’s disease, or the dominant inflammatory phenotype. In general, the microglial population does not generate a uniform response and a diverse inflammatory prolife can coexist during disease (C; CD11c⁺ vs. CD11c⁻ microglia). For all the neurodegenerative diseases considered, little evidence is available about the possible contribution of perivascular macrophages (D; CD163⁺ CCR2⁺) to the expansion/renewal of the microglial population (D; CD163⁻ CCR2⁻), although both populations have different activation and proliferation patterns. (B-D) Representative examples evidenced in prion disease, detecting microglial cells by the transgenic expression of EGFP under the c-fms promoter.