| Adu | IgG | p.overall | |
|---|---|---|---|
| N=3 | N=3 | ||
| 0 | 22.8 [21.6;23.4] | 25.6 [24.5;25.8] | 0.127 |
| 1 | 14.6 [14.6;14.9] | 19.4 [18.2;19.9] | 0.046 |
| 2 | 18.3 [17.1;18.8] | 13.7 [13.1;14.2] | 0.050 |
| 3 | 12.3 [12.1;12.4] | 11.0 [11.0;11.7] | 0.268 |
| 4 | 10.4 [10.3;11.7] | 10.9 [10.1;12.4] | 0.827 |
| 5 | 11.1 [9.70;12.1] | 11.7 [11.4;11.8] | 0.658 |
| 6 | 7.00 [4.25;7.00] | 2.40 [2.40;4.15] | 0.500 |
| 7 | 3.50 [3.20;3.65] | 2.60 [2.55;2.80] | 0.127 |
| 8 | 1.50 [1.25;1.70] | 1.40 [1.30;1.45] | 0.658 |
| 9 | 0.60 [0.45;0.80] | 0.50 [0.45;0.55] | 0.658 |
9 Differences in microglia by sample & treatment
9.1 Proportions (%) of Microglial States Across Samples and Treatments
Relative abundance of each microglial Seurat-defined cluster in individual samples and compared proportions between the Aducanumab-treated and IgG control groups.
Values are median % of microglia in that cluster per sample, with IQR.
p.overall: Mann-Whitney p-value
9.2 Pseudobulk analysis: Aducanumab vs. IgG
| p_val | avg_log2FC | pct.1 | pct.2 | p_val_adj | |
|---|---|---|---|---|---|
| H2ac20 | 0.0e+00 | -0.1750223 | 1 | 1 | 0.0000036 |
| mt-Nd4l | 0.0e+00 | -0.4711669 | 1 | 1 | 0.0001628 |
| Tnfaip2 | 0.0e+00 | -0.4571713 | 1 | 1 | 0.0001815 |
| Gm13849 | 0.0e+00 | -0.0263631 | 1 | 1 | 0.0004293 |
| Prdm1 | 1.0e-07 | -0.1948147 | 1 | 1 | 0.0020465 |
| C430049B03Rik | 2.0e-07 | -0.1446463 | 1 | 1 | 0.0032855 |
| Man1a | 2.0e-07 | -0.2427612 | 1 | 1 | 0.0042481 |
| Ccl7 | 3.0e-07 | 0.0704861 | 1 | 1 | 0.0071494 |
| Il1a | 4.0e-07 | -0.5749078 | 1 | 1 | 0.0077532 |
| Cxcl1 | 6.0e-07 | -0.2383173 | 1 | 1 | 0.0136628 |
| Dusp2 | 1.1e-06 | -0.3441218 | 1 | 1 | 0.0242598 |
| Rpl35 | 1.4e-06 | -0.3722164 | 1 | 1 | 0.0304758 |
| Mir155hg | 1.5e-06 | -0.2601184 | 1 | 1 | 0.0321594 |
| mt-Atp8 | 1.9e-06 | -0.2756153 | 1 | 1 | 0.0409223 |
| Slc38a2 | 1.9e-06 | -0.1951182 | 1 | 1 | 0.0417004 |
Following treatment, microglia from the Alzheimer’s disease mouse model exhibited a broad transcriptional shift consistent with reduced pro-inflammatory activation and metabolic demand. Several mitochondrial genes (mt-Nd4l, mt-Atp8) and the amino acid transporter Slc38a2 were downregulated, suggesting diminished oxidative phosphorylation and nutrient uptake that normally support highly activated microglial states. Key inflammatory mediators, including Il1a, Cxcl1, Tnfaip2, and the microRNA host gene Mir155hg, also decreased, indicating attenuation of cytokine release, chemotactic signaling, NF-κB pathway activity, and miR-155–driven immune activation. Concomitant reductions in Prdm1 and regulatory non-coding transcripts (Gm13849, C430049B03Rik), together with decreased Rpl35 and Man1a, point to lower transcriptional activity, protein synthesis, and secretory function, while the decline in H2ac20 implies chromatin remodeling toward a less plastic state. Notably, this general dampening of inflammatory pathways was accompanied by increased expression of Ccl7, a chemokine involved in monocyte recruitment. This suggests that while most pro-inflammatory signals were suppressed, the treatment selectively maintained or enhanced pathways favoring controlled immune cell trafficking, potentially reflecting a rebalancing of microglial responses rather than their complete silencing. Collectively, these findings support the notion that the treatment shifts microglia away from a broadly activated phenotype toward a more homeostatic yet immunologically competent state, which may contribute to mitigation of chronic neuroinflammation in Alzheimer’s disease.