Table 2.
Summary of microglial subsets reported in AD patients
| Subjects | Methods | Subsets | Signature | Conversion | Function | Publication |
|---|---|---|---|---|---|---|
| 482,472 nuclei from 18 non-demented control brains and AD brains | snRNA-seq | Homeostatic microglia |
Expressing P2RY12 and CX3CR1 |
Gerrits et al. [20] | ||
| AD-1 microglia | ↑: Phagocytic associated gene, DAM-like genes | Response to amyloid-β in the extracellular space | ||||
| AD-2 microglia | ↑: GRID2 | Response to p-tau bearing (dying) neurons | ||||
| 131,239 nuclei from 48 cases | snRNA-seq | Dystrophic microglia |
↑: Pro-inflammatory related genes ↑: FTL and FTH1 |
Nguyen et al. [108] | ||
| Amyloid-responsive microglia (ARM) |
↑: Pro-inflammatory related genes ↑: CD163, BIN1, MS4A6A, and CELF1 |
ARM subsets depend on APOE and TREM2 signaling | ||||
| Homeostatic microglia | Expressing CX3CR1 | |||||
| Motile microglia | ↑: Genes associated with cell motility, actin remodeling, and extracellular matrix remodeling | |||||
| 66,311 nuclei from 11 AD with the TREM2-CV, 10 with TREM2-R62H and 11 controls | snRNA-seq | IRF8-driven reactive microglia |
↑: TREM2, APOE, CD68, and HLA-DRA (Partial DAM) ↑: IRF8, SORL1, A2M and CHI3L1 ↑: Homeostatic gene TMEM119, P2RY12, and CX3CR1 ↓:SPP1 |
IRF8 is likely a major driver of this signature | Zhou et al. [31] |
AD Alzheimer’s disease, snRNA-seq single-nuclei RNA sequencing, DAM disease-associated microglia, ARM amyloid-responsive microglia, IRF8 transcription factor interferon regulatory factor 8, TREM2 triggering receptor expressed on myeloid cells 2