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. 2023 May 1;55(5):1023–1032. doi: 10.1038/s12276-023-00993-3

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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 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. 1 — a Overall experimental procedure. Two independent cohorts (Cohort 1, South Korean, n = 181; Cohort 2, European, n = 78) were used for this study. Cohort 1 underwent Pittsburgh compound B (PiB)-positron emission tomography (PET), fluorodeoxyglucose (FDG)-PET, magnetic resonance imaging, and blood biomarker (plasma tau and beta-amyloid 42 and 40) quantification at both baseline and at a two-year follow-up. Cohort 2 was included in a transcriptome analysis (GEO Database, GSE 109887) using human postmortem brain samples. Both analyses using Cohorts 1 and 2 had the same objective of revealing female-specific glucose metabolism changes in AD. Another publicly available dataset from the GEO database (Cohort 3, GSE150696) was also used to validate the results from Cohort 2. b, c Monotone spline models for brain imaging biomarkers in both men and women. PiB-PET SUVR was used as a proxy for the progression time of AD. To effectively show comparisons between different imaging biomarkers, their levels were transformed to z scores. d Comparison of spline slope analysis between women and men. AD Alzheimer’s disease, PiB-PET Pittsburgh compound B-positron emission tomography, SUVR standardized uptake value ratio, Hva hippocampal volume, FDG-PET fluorodeoxyglucose PET, 95% CI 95% confidence interval.