Fig. 3: Elevated GNG5 levels aggravate amyloid pathology in 5×FAD and FAD^4T mice.

A Scheme of preparing EV^RVG, GNG5@EV^RVG, and siGNG5@EV^RVG (left); schematic diagram of GNG5 intervention and subsequent behavioral examination in 5×FAD and FAD^4T mice (right). B Western blot detection of GNG5, EVs markers Lamp2b, CD63, Alix, Tsg101 and negative marker GM130 in EV^RVG and GNG5@EV^RVG. C Encapsulate efficacy of siNC and siGNG5 into EV^RVG. D Verification of GNG5 overexpression and knockdown in the cortex of 5×FAD and FAD^4T mice by ELISA. n = 10 mice per group. E–J Engineered EVs including EV^RVG, GNG5@EV^RVG, siNC@EV^RVG, siGNG5@EV^RVG were injected into mice via intravenous tail vein. WT (female, 5-month-old, n = 10), 5×FAD (female, 5-month-old, n = 10 per group), FAD^4T (female, 4-month-old, n = 10 per group). E, F Representative fluorescence micrographs and quantification of amyloid plaques (anti-6E10) and Aβ42⁺ plaques (anti-Aβ42) in cortex of indicated mice. ELISA quantification of soluble Aβ42 and Aβ40 levels in cortex (G) and hippocampus (H). I Representative fluorescence micrographs of Fluoro-Jade C staining of cortical slices. J Representative confocal images of neuronal marker NeuN⁺ labeling neurons (red) in cortex. Data are presented as the mean ± SD. p values were determined using one-way ANOVA with Turkey post hoc test for multiple groups. *p < 0.05, **p < 0.01, ***p < 0.001, ns: not significant.