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. 2023 Jul 26;28(10):4438–4450. doi: 10.1038/s41380-023-02188-8

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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. 1 — A Overall ATI(N) biomarker positivity of all included subjects for I(TSPO)-, A(Aβ)-, T(tau)- and N(perfusion, early tau)-PET at the group level. Single-region-ROC-analyses were applied to identify regions (n = 5) that discriminate best among the study groups (maximum area-under-curve) for each biomarker. For each region an individual cutoff was set based on a sensitivity/specificity tradeoff and patients were classified as biomarker-positive or –negative based on the averaged regions that allowed the most optimal discrimination. Please note that AD also includes AD pathological change according to NIA-AA. B Heterogeneity of regional ATI(N) biomarker peak distribution. The heatmap was determined by calculating arithmetic means (x̄) within 24 composed brain regions (from z-scores) and displayed in color scale. All x̄ > 2 were set equal to 2 and all x̄ < −2 were set equal to −2. The brain region with the highest z-score was determined for each study participant and the peak region frequency was plotted proportionally (%) to the number of patients in one group. C Comparison of TSPO-PET levels in patients with primary and secondary tauopathies and medium- and high-affinity TSPO binding status when compared to a mixed cohort (n = 2 AD, n = 4 4RT, n = 1 healthy control) of individuals with low-affinity TSPO binding status using the same methodological approach as in (B). D Regional ATI(N) biomarker PET signal alterations at the group level. Within each study group, the mean z-score of each Brainnetome region was calculated and plotted as surface projections (lateral and medial view) and axial slices of the basal ganglia. AD Alzheimer’s disease, AD-CBS corticobasal syndrome with AD-pathology, 4RT four-repeat tauopathies, LAB low affinity binder, CTRL healthy controls, TSPO 18-kDa translocator protein, Aβ β-amyloid, GMV gray-matter-volume, PET positron-emissions-tomography, ROC receiver-operating-characteristic.