Fig. 5: PV knockdown phenocopies chemogenetic inhibition in reducing Aβ pathology and improving memory.

A, B Schematic representation of bilateral AAV-DIO-shRNA injections for selective PV knockdown (AAV-shPV) in the subiculum of PV-Cre;5×FAD mice, with AAV-DIO-non-targeting shRNA (AAV-shNT) as a control A and the timeline of the behavioral experiments B. C Spatial learning in PV knockdown mice was assessed in the MWM over five training days (n = 10–13 mice in the three groups, two-way ANOVA with Tukey post hoc test). D-G Quantification of time spent in the target quadrant D, latency to first entrance to the platform zone E, number of target crossings F, and average swim speed G during the probe trial of the MWM (n = 10–13 mice in the three groups, one-way ANOVA with Tukey post hoc test). H, I Representative images showing PV knockdown in the subiculum and Aβ immunohistostaining H. Yellow arrows indicate co-localization of AAV-infected cells and PV-positive neurons. Quantification of PV-positive cells and Aβ-positive plaques I (n = 6–10 slices from 3–4 mice per group, unpaired t-test). J PVALB expression in GABAergic interneurons from patients across different Braak stages. Data are from 84 patients: 2 Braak 0 (12,107 neurons), 4 Braak II (16,721 neurons), 6 Braak III (23,985 neurons), 23 Braak IV (104,513 neurons), 34 Braak V (112,116 neurons), and 15 Braak VI (51,150 neurons). Data obtained from the SEA-AD dataset. All data are represented as mean ± SEM. ns not significant, *p < 0.05, ****p < 0.0001.