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Table 2 Summary of microglial subsets reported in AD patients

From: Pathogenesis, therapeutic strategies and biomarker development based on “omics” analysis related to microglia in Alzheimer’s disease

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]

  1. 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