Figure 1.

A schematic showing a hypothetical dual role for disease-associated microglia (DAM) in the progression of Alzheimer's disease (AD). The x-axis corresponds to time in years. Time 0 indicates the onset of symptomatic AD (i.e., mild cognitive impairment). The bottom panel depicts changes in the relative expression of genes upregulated and downregulated by DAM. These changes are associated with the transition from immunosuppressive phagocytosis to immunoreactive inflammation (Saito and Saido, 2018). The bottom y-axis represents the relative expression of immunosuppressive and immunoreactive genes regulated by DAM (e.g., TREM2 and C3). The top panel portrays non-DAM and DAM that are clustered according to their distinct transcriptional profiles (Keren-Shaul et al., 2017). The top y-axis outlines the functionally different populations of microglia (e.g., non-DAM, neuroprotective DAM, and neurotoxic DAM).