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. 2021 Nov 11;18(4):2484–2503. doi: 10.1007/s13311-021-01151-1

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© The Author(s) 2021

Open AccessThis 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. 3 — Systemic administration of the AAV-hE2F4DN vector reduces Aβ production and accumulation in the hippocampus in h5xFAD mice. (a) Representative western blot of hippocampal extracts from wild-type (WT) and h5xFAD mice of 2, 4.5, and 6.5 months of age administered with either AAV-EGFP (EGFP) or AAV-E2F4DN (E2F4DN) at 1.5 months, revealed with anti-Aβ, APP or Lamin B1 (loading control) antibodies. Asterisk: Aβ band (4 kDa). Arrow: processed Aβ monomers. (b, c) Ratio with Lamin B1 of Aβ monomer (4 kDa; b) or APP (c) in hippocampal extracts from h5xFAD mice administered with either AAV-EGFP (EGFP) or AAV-E2F4DN (E2F4DN) at the indicated ages. A significant correlation with time was observed for the level of Aβ monomer in both experimental situations. A statistically significant decrease of the regression slope was observed in E2F4DN-treated mice (t = 4.651209, p = 0.00164210; t test). N.S. = nonsignificant. (d) Aβ amyloid deposits in the hippocampus of 6.5-month-old h5xFAD mice administered with either vehicle or AAV-E2F4DN (hE2F4DN) at 1.5 months, stained with thioflavin S (arrows). DG = dentate gyrus; CA1 = cornu ammonis 1; Sub = subiculum. Scale bar, 50 μm. (e) Quantification of percentage of total area occupied by the Aβ deposits in the hippocampus. *p < 0.05 (two-tailed Student’s t test)