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. 2023 Nov 30;14:7659. doi: 10.1038/s41467-023-43132-2

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© The Author(s) 2023

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 licence, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons licence 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 licence, visit http://creativecommons.org/licenses/by/4.0/.

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Fig. 2 — a Association of cell-type-specific ADPRSs with the odds of AD with dementia (case: n = 538, control: n = 248). b Association of cell-type-specific ADPRSs with overall Aβ burden. c Association of cell-type-specific ADPRSs with overall diffuse plaque (DP) burden. d Association of cell-type-specific ADPRSs with overall neuritic plaque (NP) burden. e Association of cell-type-specific ADPRSs with overall paired-helical-filament tau (PHFtau) burden. f Association of cell-type-specific ADPRSs with overall neurofibrillary tangle (NFT) burden. g Association of cell-type-specific ADPRSs with cognitive decline (the slope of annual change in antemortem measures of global cognitive composite). For a–g, the y-axis indicates -log₁₀(p-value) of each association, the black solid horizontal line indicates the p-value corresponding to multiple comparisons-corrected statistical significance (FDR = 0.025), and the black dashed horizontal line indicates p = 0.05. The p-values (two-sided, unadjusted) are from regression models (a logistic regression, b–g linear regression) adjusting for APOE ε4, APOE ε2, age at death, sex, genotyping platform, years of education (only for a and g), and the first three genotyping principal components. The effect size of each statistically significant PRS-trait association was quantified with ΔR² (difference of Nagelkerke’s R² (a) or adjusted R² (b–g) between the linear models with and without the given PRS term; b–g) and indicated above the bar graph. Also, see Supplementary Tables 3–9 for further details. Source data are provided as a Source Data file. h Association of Mic-ADPRS (x-axis) and the proportion of activated microglia (PAM, y-axis). On y-axis, residual PAM values adjusting for covariates (APOE ε4, APOE ε2, age at death, sex, genotyping platform, and the first three genotyping principal components) were shown. T-statistics and p-values from linear regression (adjusting for the covariates) are shown. Created with Biorender.com. Act. Mic. activated microglia, All full autosomal genome, Ast astrocytes, Ex excitatory neurons, In inhibitory neurons, Mic microglia, Oli oligodendrocytes, Opc oligodendroglial progenitor cells.