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. 2024 Oct 11;15(10):744. doi: 10.1038/s41419-024-07062-1

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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 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. 4 — a A workflow diagram of NMN (500 mg/kg, intraperitoneal injection) treatment began at 3.5-month-old mice for 2 months. b–g The behavioral test results of 6-month-old mice. Data were analyzed by two-sided one-way ANOVA followed by Tukey’s multiple comparisons test. b The representative swimming tracks of mice from a probe trial day (n = 16 mice in WT (VEH), n = 16 mice in AD (VEH), n = 13 in WT (NMN), and n = 16 in AD (NMN)). c Spatial memory analysis of each group. Left, time in the target quadrant in the probe trial; center, platform frequency of mice passed through the platform in the probe trial at day 7; right, latency to escape to a hidden platform in the MWM during a 6-day training period. Data were analyzed by two-way ANOVA followed by Tukey’s multiple comparisons test. d–g New object recognition (d), Y maze (e), Open Field test (f), and contextual and cued fear conditioning (g) tests were performed. h, i The behavioral tests analysis as in (b–g) in 12-month-old mice (n = 13 mice in WT (VEH), n = 7 mice in AD (VEH), and n = 7 in AD (NMN)). New object recognition (i) and open Field test (h) tests were performed. j–l The results of MWM in each group in 12-month-old mice. Data were analyzed by one-way ANOVA followed by Tukey’s multiple comparisons test for (h–k), while two-way ANOVA was used for (l). m Effects of NMN on the expression levels of APP and its indicated metabolites, BACE-1, and CTFs hippocampal tissues from 5xFAD. Full-length APP, C99, and Aβ were detected with 6E10 antibody (n = 6 mice per group; one-way ANOVA). n Confocal images of 4G8+ GFAP+ double-positive cells from hippocampi of 6-month-old WT, 5xFAD and 5xFAD (NMN) mice. Insets were enlarged from hippocampal areas. Scale bar, 100 μm. The experiments were repeated from three independent experiments with the results shown as mean ± s.e.m. o Soluble and insoluble Aβ_1–40 and Aβ_1–42 levels in hippocampal tissues (n = 9 mice; two-sided unpaired t-test). All experiments were performed independently with at least three biological replicates. Data are shown as mean ± s.e.m. The p-values are indicated on the graphs. ns not significant.