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. 2022 Feb 3;25(2):213–225. doi: 10.1038/s41593-021-00999-y

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© The Author(s) 2022

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. 5 — a–c, TMT AD network modules associated with cognitive decline (a) or cognitive preservation (b) after adjustment for ten neuropathologies in ROSMAP. Eigenprotein values are plotted against the rate of cognitive change during life for each participant in ROSMAP (n = 328). Decline is highlighted in red; preservation is highlighted in blue. β is the effect size of module eigenprotein on cognitive trajectory after adjustment for neuropathology; q is the FDR significance level of this effect. Shaded areas represent 95% confidence intervals for β values. Information on the association between all TMT AD network module eigenproteins and cognitive trajectory before and after adjustment for neuropathology is provided in Supplementary Table 27. c, TMT AD network module enrichment of proteins positively associated with cognitive resilience (that is, preservation) or negatively associated with cognitive resilience (that is, decline) identified in a previous PWAS of cognitive resilience in the ROSMAP cohort⁴¹. The dashed red line indicates a Z score of 1.96 (P = 0.05), above which enrichment was considered significant. Modules that are shaded are consistent with results in a and b. Modules are ordered by relatedness as illustrated in Fig. 1b. MHC, major histocompatibility complex.