Fig. 2: Reduced ALDH2 activity significantly increased the Aβ40/42 ratio.

a Schematic image of the endogenous loci to generate Aldh2-knockout mice in a C57BL/6 background. (Image was created using Photoshop CS6, with elements from ChemBioDraw Ultra software 14.0.) b WB confirmed the Aldh2 expression in Aldh2 ^−/− mouse brains. All mice with Aldh2^−/− showed similar results. c Levels of Aβ42 and Aβ40 peptides in cortex (COR) homogenates from 3-month-old Aldh2^−/− mice (n = 5 mice) and age-matched wild-type mice (n = 4 mice) by ELISA. d Scheme illustrating intragastric administration of daidzin (150 mg/kg/day) in 2-month-old APP/PS1 mice for 2 months. Aβ pathology was assessed in 7-month-old mice. (Image was created using Photoshop CS6 and ChemBioDraw Ultra software 14.0.) e Immunohistochemical staining of Aβ plaque deposits in COR and Hipp and f quantification of Aβ40 and Aβ42 levels in COR from APP/PS1 transgenic mice with phosphate-buffered saline (PBS, n = 4 mice) or daidzin administration (n = 4 mice). g and h ALDH2 knockdown by siRNA or daidzin (30–100 μM) treatment for 48 h in SH-SY5Y cells. g Enzymatic activity of ALDH2 in cell lysates, measured over 120 min by using a mitochondrial aldehyde dehydrogenase (ALDH2) Activity Assay Kit (Abcam, ab115348). n = 3 biologically independent samples. h Levels of intracellular Aβ42 and Aβ40 peptides. n = 3 biologically independent samples. i–k ALDH2 functional deficiency caused by ALDH2 silencing or combined with daidzin co-treatment for 48 h in HEK293T cells. i RT-qPCR of relative ALDH2 mRNA levels (n = 3 biologically independent experiments) and j WB detection of ALDH2, APP, and PS1 expression levels. k Levels of intracellular Aβ42 and Aβ40 peptides. n = 3 or 4 biologically independent samples. siNC negative control small interfering RNA. Data are presented as mean values ± SD. All box plots include the median line, the box indicates the interquartile range, and whiskers indicate minima and maxima. Statistical analysis was performed using a two-tailed Student’s t-test for two groups (c, e, f, h, i, k) and one-way ANOVA with LSD post-hoc test for multiple groups (h). Source data are provided as a Source Data file.