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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. 6 — Systemic administration of the AAV-hE2F4DN vector prevents memory deficits and clasping behavior in h5xFAD mice. (a) Percentage of alternation in the Y-maze test of 3-month-old h5xFAD transgenic mice subjected to systemic administration of the AAV-EGFP control vector or the AAV-hE2F4DN vector. (F_(3,45) = 3.75619, p = 0.017; one-way ANOVA; WT/EGFP vs h5xFAD/EGFP: q = 13.742, p = 0.036; h5xFAD/EGFP vs h5xFAD/hE2F4DN: q = 10.204, p = 0.043; Tukey’s HSD post hoc test). (b) Number of arms entered in the Y-maze test of 3-month-old h5xFAD transgenic mice subjected to systemic administration of the AAV-EGFP control vector or the AAV-hE2F4DN vector. (F_(3,45) = 0.20931, p = 0.889; one-way ANOVA). (c) Analysis of paw-clasping behavior in h5xFAD mice of 9 months, either noninjected (N-I) or injected with AAV-EGFP (EGFP) or AAV-hE2F4DN (hE2F4DN). (h5xFAD/EGFP vs h5xFAD/hE2F4DN: K(9) = 4.267, p = 0.039; Kruskal–Wallis test). (d) hE2F4DN expression prevents spatial memory impairment in homozygous 5xFAD mice as evaluated by the MWM test at 6 months of age. Latency time to reach the hidden platform along four training days in homozygous 5xFAD mice either noninjected or injected with the AAV-hE2F4DN vector and in noninjected wild-type mice (left). Statistical significant differences between WT and h5xFAD mice, but not between WT and h5xFAD mice administered with AAV-E2F4DN, were observed at training day 4 (F_(2,15) = 4.0569, p = 0.039; one-way ANOVA; h5xFAD vs WT: q = 16.4475, p = 0.037; Tukey’s HSD post hoc test]. No statistically significant differences among experimental groups were observed for velocity of swimming (one-way ANOVA) (right). *p < 0.05 (Tukey’s HSD post hoc test)