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. 2022 Apr 25;2(6):526–535. doi: 10.1038/s43587-022-00204-0

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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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Extended Data Fig. 5 — Top: Individual neurodegeneration biomarkers represented with 95% Confidence Intervals. MRI-measured hippocampal volume (adjusted for intracranial volume) increased in severity starting at stage II onwards (n = 324 individuals). Fluid neurodegeneration biomarkers increase with advancing PET-based Braak stage. CSF measurements of SNAP-25 (long) and neurogranin increased at stages III–IV (189 individuals with CSF measurements). No differences were observed between stages 0, I and II. Substantial within-stage variability was observed for plasma NfL (n = 292 individuals). No differences were observed between stages 0, I and II. Both fluid and imaging neurodegeneration biomarkers showed substantial within-stage variability, potentially reflecting the fact that neurodegeneration is a multifactorial process, influenced by factors other than tau-mediated neurodegeneration. Bottom: Neurodegeneration biomarker curves superimposed according to PET-based Braak stage. Note that Hippocampal volume was inverted in order to compare the degree of abnormality.