Fig. 5

TA1 enhances the autophagic degradation of Aβ and reduces Aβ pathology in APP/PS1 mice. 6-month-old APP/PS1 mice were administered TA1 orally at 10 mg/kg for 3 months. A, B Mice brain sections were probed with anti-Aβ1–16 (6E10) antibodies. Scale bar = 2 mm. The number of hippocampal and cortical plaques was quantified in twelve evenly spaced brain slices from each mouse. n = 8, 6 (Student's t test). C Aβ1–42 in brain tissues was determined using ELISA. n = 6 (Student's t test). D Brain sections were co-stained with anti-TFEB and anti-Iba1 antibodies. Arrows indicate the PAM nuclei. Scale bar = 25 μm. E–H Brain sections were co-stained with anti-LC3, anti-Iba1, and anti-Aβ1–16 (6E10) or anti-LAMP1 antibodies. Scale bar = 10 μm. The colocalization ratio of LC3 with Aβ or LAMP1 in Iba1⁺ cells were estimated via Manders' colocalization coefficients. n > 30 (Student's t test). I, J Primary microglia were co-treated with oAβ and TA1 for 12 h, followed with bafilomycin A1 treatment for 1 h. Then, cells were probed with anti-LC3 and anti-LAMP1 antibodies. Scale bar = 5 μm. The colocalization ratio of LC3 with LAMP1 in single cell was quantified using Manders' colocalization coefficients. n > 40 (two-way ANOVA). K Aβ1–42 in the medium were then detected using ELISA. n = 5 (Student’s t test). L–O After co-treated with oAβ and TA1, cells were incubated with Aβ-555 for 30 min, or co-treated with bafilomycin A1 for 30 min and chased. Then, cells were stained with anti-LC3 or anti-LAMP1 antibodies. Scale bar = 5 μm. The colocalization ratio of Aβ-555 with LC3 or LAMP1 was measured via Manders’ colocalization coefficients. n > 50 (two-way ANOVA). *P < 0.05, **P < 0.01, and ***P < 0.001. TG, APP/PS1 transgenic mice