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. 2019 Aug 21;10:3758. doi: 10.1038/s41467-019-11674-z

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© The Author(s) 2019

Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.

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Fig. 9 — Microglia mediate downregulation of neuronal/plasticity genes in the hippocampus in response to AD pathology. a Venn diagram showing the number of differentially expressed genes (adjusted (adj.) p < 0.05) for cortex, hippocampus, and thalamus for wild-type (WT) vs. 5xFAD mice. b Heatmap of the adj. p-value and log(2) fold change for all 9 comparison groups (5xFAD vs. WT in cortex, hippocampus, or thalamus, 5xFAD + PLX5622 vs. 5xFAD in cortex, hippocampus, or thalamus, and WT + PLX5622 vs. WT in cortex, hippocampus, or thalamus), as well as 3 comparisons between brain regions for both WT and 5xFAD mice, for the transgene components in 5xFAD mice (App, Psen1, Thy1). c Heatmap of all 413 gene expression differences identified in the hippocampus for wild-type vs. 5xFAD, expressed as log (2) fold change, and all 9 comparison groups included. Hippocampus for 5xFAD vs. WT and 5xFAD + PLX5622 vs. 5xFAD highlighted by red border, showing that most significant gene expression changes induced by pathology do not occur in the absence of microglia. d Downregulated genes in the hippocampus from (a), displayed as a heatmap of log(2) fold change differences for all 9 comparisons, showing that the same genes are not downregulated in the absence of microglia (5xFAD + PLX5622 vs. 5xFAD Hip). e RPKM values plotted on a log(2) scale for a subset of plasticity genes from (d). f Five significantly upregulated and downregulated pathways for 5xFAD vs. wild-type hippocampus (red), along with respective -log(10) p-values plotted: most upregulated pathways are related to immune function, while downregulated pathways are mainly associated with neuronal and synaptic activity. The same pathways are displayed for the comparison between 5xFAD + PLX5622 vs. 5xFAD hippocampus (yellow), showing that the absence of microglia prevents the upregulation of immune pathways and the downregulation of synaptic pathways. Expression difference denoted by *. Log(2) fold change and p-values indicated by respective scale bar. n = 4 per group for all analyses. Error bars indicate SEM