Table 4.
Examples of expression changes in mouse models with Alzheimer-type pathology.
| References | Mouse Model | # Up genes | Examples of ups | Up Pathways | # Down genes | Examples of downs | Methodology and Tools |
|---|---|---|---|---|---|---|---|
| 87 | PS2APP; 7, 13 months | Bulk: 85 (66 imputed to microglia)/Isolated microglia: 215 | CCL3; Clec7a; Trem2; Apoe; Igf1 | Not discussed | Bulk: 0 Isolated microglia: 34 | Bulk: 0 Isolated microglia: Clec4a3; Irf4 | Cortex + HPC; percoll gradient separation; RNAseq |
| 65 | 5xFAD; 1, 3, 6, 8 months | 145 in DAM vs homeostatic microglia | Apoe; Axl; Csf1; Clec7a; Cst7; Gpnmb; Igf1; Itgax; Spp1; Trem2 | lysosomal/phagocytic pathways; endocytosis; regulation of immune response | Cx3cr1; P2ry12; Tmem119 | Percoll gradient separation; Cd45+ cells sorted; single cell RNAseq | |
| 66 | APP-PS1; 9, 24 months | 28 in MGnD vs homeostatic microglia | Apoe; Axl; Ccl2; Csf1; Clec7a; Itgax; Lilrb4; Spp1 | 68 | Cx3Cr1; Csf1r; Egr1; Gpr34; Olfml3; P2ry12; Sall1; Tgfb1; Tmem119 | Percoll gradient separation; Fcrls+ cells sorted; single cell RNAseq or microarray | |
| 76 | CK-p25 inducible neurodegeneration | 202/278 DAM genes | MHC-I; MHC-II; Irf7; Ifitm3 | Proliferation early; immune response later; interferon response | HPC; Cd11b+/Cd45+ cells sorted; single cell RNAseq; | ||
| 75 | PS2APPxCx3cr1-GFP, 14-15 months; hMAPT-P301L, 12 months; hMAPT-P301S, 6 months | Neurodegeneration module with 134 genes | Apoe; Axl; Clec7a; Csf1; Cst7; Igf1; Itgax; Spp1 | Plasma membrane; extracellular space | Homeostatic genes | Cortex or HPC; Cx3cr1+ cells sorted | |
| 71 | rTg4510 (hMAPT-P301L); 2, 4, 6, 8 months | 293-2101 depending on age | Apoe; C1qa, b, c; C3; Clec7a; Itgax; Trem2 | Innate immune activation; lysosome/phagosome | 75-1588 depending on age | Glutamate synapse | Forebrain; percoll gradient separation or Cd11b+ MACS selection; RNAseq |
| 90 | APP-NL-G-F (APP KI); 3, 6, 12, 18 months | 57 amyloid plaque induced genes (PIGs); A majority, but not all, PIGs are microglial genes | 18 in common with DAMs= Apoe; Hexa; Trem2; Tyrobp Others = Axl; C1qa; Clu; Csf1r; Cst3; Cx3cr1; Grn; H2-D1; H2-K1; Hexb; Olfml3 | classical complement cascade activation; endocytosis; lysosomal degradation; antigen processing and presentation; immune response; oxidation/reduction processes | Spatial transcriptomics; in situ sequencing | ||
| 42 | APP-NL-G-F; 3, 6, 12, 21 months | Identified ARM | Cst7; Clec7a; Gpnmb; Itgax; Spp1 | Cortex or HPC; Cd11b+ cells sorted; single cell RNAseq | |||
| 68 | APPswe/PS1-L166P; Tau22; 4, 10-11 months | 287 in APPswe/PS1-L166P; 47 in Tau-22 | Apoe; Clec7a; Cst7; Itgax; Tyrobp | Aβ-induced transcriptional response; immune response; cytokine production; inflammation | P2ry12; Tmem119; Nav2 | 77 in Tau22, primarily neuronal origin | HPC; Cd11b+/Cd45+; RNAseq |
| 38 | 5xFAD; Trem2−/−x5xFAD; 7,10, 15 months | Apoe; Cst7, Csf1; Lpl; Trem2; MHC-1, MHC-II, cathepsins | P2ry12; Selplg; Tmem119; Cx3cr1 | HPC, Cortex; snRNAseq |
Abbreviations: APP, amyloid precursor protein; ARM, activated response microglia; DAM, disease-associated microglia; FACS, fluorescent cell sorting; HPC, hippocampus; KI, knock in; MACS, positive cell selection using magnetic beads; MGnD, microglial neurodegenerative phenotype; PS, presenilin