Fig. 2: Comparison of astrocytes in tau and amyloid pathology with acutely induced reactive profiles, ageing astrocytes, and AD risk genes.

A Example images of phospho-tau and NeuN staining of spinal cord sections at the indicated ages and genotypes, illustrating progressive accumulation of phospho-tau and neurodegeneration as previously reported10. Scale bar: 100 µm. B (Left) Genes induced >1.5 fold at 5 months in the MAPTP301S mouse (expression cut-off 1FPKM, Benjamini–Hochberg p_adj<0.05) were taken and enrichment analysis performed on the indicated gene sets (see main text for details). Fold enrichment is shown, and 95% confidence interval (CI) of the fold enrichment depicted by the error bar. *p values (left-to-right, here and throughout the manuscript): 5.3E−07, 4.2E−22, 8.3E−42 1.7E−06, 2.6E−12, 5.6E−14, 1.2E−19 (two-sided Fisher’s exact test). B (right) Genes induced >1.5 fold at 5 months in the MAPTP301S mouse (expression cut-off 1FPKM, Benjamini–Hochberg p_adj < 0.05) were taken and enrichment analysis performed on human genes of different p value cut-offs for association with late-onset AD21. P values: 0.082. 0.9. 0.29, 0.075, 0.90. C Example images of amyloid plaques (ThioS) and neurons (Neurotrace) staining of cortical sections at the indicated ages of the APP/PS1 mouse, illustrating progressive accumulation of plaques and lack of neurodegeneration as previously reported91. Scale bar: 300 µm (main picture); 20 µm (inset). D (left) Genes induced >1.5 fold at 12 months in the APP/PS1 mouse (expression cut-off 1FPKM, p_adj < 0.05) were taken and enrichment analysis performed exactly as in B (left), with fold enrichment is shown, and 95% CI depicted by error bar. *p values: 4.1E−06, 6.0E−06, 3.5E−15, 2.0E−05, 0.0006, 3.0E−08, 3.1E−09 (two-sided Fisher’s exact test). D (right). Enrichment analysis of genes induced >1.5 fold at 12 months in the APP/PS1 mouse for human genes of different p value cut-offs for association with late-onset AD. *p values: 0.011, 0.028, 0.017, 0.020; 0.63 (ns) (two-sided Fisher’s exact test).