Fig. 5.

Cell-type-specific promoter methylation of the PEN-2 gene in dentate gyrus (DG) across individuals with different NIA-AA A scores. a Scatterplots with smoothers showing the relationship between neuronal methylation of the promoter region of the PEN-2 gene (y-axis) across the five different cell types and bulk data from individuals with different Aβ plaque burden (NIA-AA A scores, x-axis). Methylation beta values are displayed on the y-axis and the categories of the NIA-AA A score on the x-axis. Each individual plot shows data from the dentate gyrus (DG) for different cell types. Each dot represents one individual sample. The standard linear regression was plotted as smoothers on top of the data: Smoothers curves are showing the relationship (solid line) between the NIA-AA A score and the methylation beta-value. Shaded areas indicate the 95% confidence interval of the smooth curve. We saw significant hypomethylation (**FDR p = 0.001, logFC = 0.80) in the promoter region of the PEN-2 gene with increasing Aβ plaque burden in the dentate gyrus. b Immunohistochemistry (IHC) of PEN-2 in the hippocampal region Cornu Amonis 3 (CA3) of an individual with high Alzheimer’s disease neuropathological changes (AD severity score = 3). IHC Scoring 3+ . The respective participant was Participant 44; for extended phenotype data of this individual see Additional File 4. Olig/OPCs Oligodendrocytes/Oligodendrocyte Precursor Cells. DG Dentate gyrus, Aβ Amyloid beta