Figure 4.

Gfa2–VIVIT reduces Aβ pathology in Tg mice. A, B, Representative photomicrographs (scale bar, 100 μm) and accompanying plaque load analysis (C, mean ± SEM) illustrating differences in the immunohistochemical labeling of Aβ deposits (brown) in Tg Ct and Tg VIV mice. Hematoxylin (blue) labels the pyramidal neuron layer in CA1. D–F show ELISA measures (mean ± SEM) of soluble, insoluble, and total (soluble + insoluble) Aβ_(1–42) peptide levels in hippocampal homogenates of Tg mice. The Gfa2–VIVIT-treated group showed significantly lower (*p < 0.05) total peptide levels (F), attributable mostly to a significant reduction in the toxic, soluble Aβ fraction (D). G–J, Representative Western blots (G) and mean ± SEM protein levels (H–J) for Aβ metabolic enzymes measured from hippocampal homogenates of WT Ct, WT VIV, Tg Ct, and Tg VIV mice. Values are normalized to GAPDH internal controls and expressed as a percentage of the WT Ct group. H, BACE1, the rate-limiting enzyme in Aβ production, was differentially affected by VIVIT treatment across genotypes (^#p < 0.01 Tg Ct vs Tg VIV; *p < 0.05 WT Ct vs WT VIV). I, J, IDE and neprilysin, participants in amyloid clearance, were not affected by VIVIT treatment, although neprilysin did show a genotype difference (⁺p < 0.001 Tg Ct and Tg VIV vs WT Ct).