Fig. 7: Lower ALDH2 activity ameliorated Aβ-induced microglial activation and phagocytic phenotype.
From: The aldehyde dehydrogenase 2 rs671 variant enhances amyloid β pathology
a and b Representative images of BV2 cells with Aldh2 silencing, followed by treatment with lipopolysaccharide (LPS) (1 μg/mL), oligomeric Aβ40 (oAβ40, 1 μM), or fibrillar Aβ40 (fAβ40, 1 μM) for 24 h. a Bright-field images and quantification of activated BV2 cells. Scale bar, 50 μm. n = 6 randomly selected fields per group. b Fluorescence microscopy of activated BV2 cells labeled with Alexa Fluor 488 phalloidin (green). Scale bar, 10 μm. c Relative Il−1β, Il-6, and Tnf-α mRNA levels in wild-type BV2 cells treated with oAβ40 (1 μM) or fAβ42 (1 μM) for 0, 2, 4, 6, 8, and 12 h, respectively. n = 3 biologically independent samples. d Relative Il-1β, Il-6, and Tnf-α mRNA levels in BV2 cells with Aldh2 knockdown and treatment with LPS (100 ng/mL), oAβ40 (1 μM), or fAβ42 (1 μM) for 4 h. n = 3. e Flow cytometry histogram showing the phagocytosis rate of BV2 cells with Aldh2 knockdown, stimulated with oAβ40 (1 μM) for 24 h and then co-incubated with latex beads for 4 h. n = 3 biologically independent samples. The flow-cytometry gating strategies were shown in Supplementary Fig. 13c. f Representative images of Aβ plaques (6E10, green) and microglia (Iba-1, red) in the cortex from APP/PS1 mice and daidzin-treated APP/PS1 mice. Quantification of microglial cells within 20 μm of a plaque (n = 28 plaques from 3 mice per group). Scale bar, 20 μm. g Representative images of Aβ plaques (6E10, green) and microglia (Iba-1, red) in the prefrontal lobe from pathological AD with rs671 GG genotype (n = 3) or the GA/AA genotype (n = 3). Quantification of microglial cells within 20 μm of a plaque (n = 24–28 plaques from 3 brains with AD per group). Scale bar, 20 μm. siNC negative control small interfering RNA. Data are presented as mean values ± SD. Statistical analysis was performed using one-way ANOVA with LSD post-hoc test for multiple groups (a, d) or two-tailed Student’s t-test for two groups (e–g). Source data are provided as a Source Data file.
