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. 2023 Feb 20;3(3):275–296. doi: 10.1038/s43587-023-00368-3

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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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Extended Data Fig. 2 — a–c, Total tau levels measured by ELISA in the hippocampal lysates of 10-month-old PS19-fE4 and PS19-fE3 mice with and without Cre, following sequential biochemical extraction in RAB and RIPA buffer (PS19-fE4: No Cre, n = 21; Syn1-Cre, n = 19; PS19-fE3: No Cre, n = 17; Syn1-Cre, n = 11). Total tau levels were normalized to the weight of the dissected hippocampal tissue for each individual mouse. d, Representative images of the injected and non-injected hippocampal sides of a 10-month-old fE4 mouse 2 weeks after a unilateral injection with an AAV2-GFP virus and immunostained with anti-GFP (scale bar, 500 µm). e, Representative high magnification images of the injected and non-injected hippocampal sides of a fE4 mouse 2 weeks after an unilateral injection and immunostained with anti-GFP and DAPI (scale bar, 100 µm). f, Quantification of percent HT7 (human tau) coverage area on the injected hippocampal side. g, Quantification of number of AT8-positive neurons in the neuronal cell layer on the injected hippocampal side. h, Normalization of the number of AT8-positive neurons on the injected hippocampal side to the percent HT7 coverage area on the injected hippocampal side. i, Normalization of the number of HT7-positive neurons on the non-injected hippocampal side normalized to the percent HT7 coverage area of the injected hippocampal side. j, Normalization of the number of AT8-positive neurons on the non-injected hippocampal side to the percent HT7 coverage area of the injected hippocampal side. Mice used in f–j are 13-month-old fE4, fE4/Syn1-Cre, and fE3 mice (n = 8 per group). k, Representative images of HT7 immunostaining on the injected hippocampal side of 13-month-old fE mice with or without Cre (scale bar, 500 µm). l, Representative images of AT8 immunostaining on the injected hippocampal side of 13-month-old fE mice with or without Cre (scale bar, 500 µm). White arrows in l indicate neuronal soma areas in hippocampi. Data in a,b,c,f,g,h,i,j are represented as mean ± SEM, one-way ANOVA with Tukey’s post hoc multiple comparisons test.

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