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. 2020 Mar 12;139(6):1025–1044. doi: 10.1007/s00401-020-02138-6

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© The Author(s) 2020

Open AccessThis 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. 4 — Role of p.P522R in the interrelationship between amyloid pathology, neurodegeneration, and cognitive decline. a Predicted relationship between Aβ_1-42 levels in CSF and pTau₁₈₁ levels in CSF for p.P522R carrier and non-carrier. Red shaded areas indicate significant differences between p.P522R carrier and non-carrier. Significance is based on the estimation of simultaneous confidence intervals that consider the statistical testing at multiple CSF levels. b Predicted relationship between Aβ_1-42 levels in CSF total tau levels in CSF for p.P522R carrier and non-carrier. Red shaded areas indicate significant differences between p.P522R carrier and non-carrier. Significance is based on the estimation of simultaneous confidence intervals that consider the statistical testing at multiple CSF levels. c Results from a structural equation model assessing whether the effect of p.P522R on the cognitive change in the normalized MMSE (range 0–100) is mediated Abeta_1-42 levels or pTau₁₈₁ levels in CSF. The model showed a good fit to the data (Model fit indices: RMSEA = 0.017, CFI = 0.996, SRMR = 0.060, see supplementary text 6.4, online resource)