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. 2024 Feb 16;15:1434. doi: 10.1038/s41467-024-45692-3

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© The Author(s) 2024

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. 8 — a Representative confocal images of AT8 and PGRN co-staining of NFTs and NPs in the anterior hippocampus region of AD brain. Bar, 20 μm. Similar results were obtained in at least two other free-floating AD samples (S15147 and S19475) and one paraffin-embedded AD sample (VGH-2, shown in Supplementary Fig. 20b). b Representative confocal images of AT8 and GlcCer co-staining of NFTs and NPs in the anterior hippocampus region of AD brains. Arrowheads indicate GlCer labeling of some of NPs. Bar, 20 μm. c Representative confocal images of AT8 and GlcCer co-staining of NFTs and LBs in the anterior hippocampus region of DLB brains. Bar, 20 μm. d Quantification of percentage of GlcCer+ aggregates of NFTs of AD, AH2, DLB brains and LBs of DLB brain tissue. At least 10 NFTs were examined in each sample except for two DLB samples due to the low numbers of NFTs (2 and 6 NFTs). The mean number of NFTs examined in each group is as follows: AD = 15 ± 1.924, AH2 = 13.75 ± 1.652, DLB = 8.5 ± 2.986. At least 11 LBs were examined for each DLB brain, and the mean number is 14 ± 1.472. Mean ± SEM, n = 5 brains (AD, NFTs), n = 4 brains (the other groups) ****p = 0.000000000004; One-way ANOVA with Tukey’s post hoc test. e Representative confocal images of AT8 and GlcCer or GCase of co-staining of NPs in the middle frontal gyrus of an FTD-GRN brain. Bar, 20 μm. An arrowhead indicates co-localization of GCase with AT8-positive neuritic plaques. An arrow indicates glial localization of GCase. An asterisk indicates lysosomal GCase in neurons. Bar, 20 μm. f Representative confocal images of AT8 and GCase of co-staining of NFTs in the hippocampus of AD and FTD-GRN brain. Bar, 20 μm. g Quantification of percentage of AT8+ GlcCer+ aggregates of NFTs in the hippocampus of AD and FTD-GRN brain. NFTs of AD were divided into two groups: mature and immature NFTs, based on their morphology. At least 48 NFTs for each group were examined in each sample except for one FTD-GRN sample due to the low number of NFTs (15 NFTs). The mean number of NFTs examined in each group is as follows: AD, mature NFTs = 56.25 ± 3.75, AH2, immature NFTs = 58.00 ± 4.673, FTD-GRN NFTs = 35.5 ± 20.50. Mean ± SEM, n = 4 patients (AD, mature NFTs and AD, immature NFTs), n = 2 (FTD-GRN, NFTs), *p = 0.0202 (AD, mature tangles vs. AD, immature tangles), *p = 0.0253 (AD, mature tangles vs. FTD-GRN, tangles); One-way ANOVA with Tukey’s post hoc test. Source data are provided as a Source Data file.