Excel spreadsheet containing detailed data matrices supporting all figures in the study.

Complete annotations for the tabular data are presented below. Tab Fig 1: (A) The heatmap data of G protein family members in the hippocampal tissue of 6-month-old Wildtype (n = 6) and 5xFAD (n = 6) mice; (B) The heatmap data of G protein family members in the cortical tissue of 6-month-old Wildtype (n = 6) and 5xFAD (n = 6) mice; (C) The data in the overlapping part of the Venn diagram (132 elements); (D) The data information for creating volcano plot; (E) The data information for creating heatmap of GPCR-related DEGs; (F) Expression of Gnb5 in the large sample dataset GSE44772; Control, n = 303; AD, n = 387; (H) Statistical analysis of Gnb5 protein levels from panel G; Wildtype, n = 4; 5xFAD, n = 4; (J) Statistical analysis of Gnb5 protein levels from panel I; Wildtype, n = 4; 5xFAD, n = 4; (L) Quantitative analysis of Gnb5 fluorescence intensity in 5xFAD and Wildtype groups; Wildtype, n = 4; 5xFAD, n = 4. Tab Fig 2: (D) qPCR data of Gnb5 knockout in hippocampal tissue; Gnb5F/F, n = 6; Gnb5-CCKO, n = 6; (E–I, L–N) Animal behavioral tests in mice, Gnb5F/F, n = 22; Gnb5-CCKO, n = 16; (E) Total distance traveled in the open field experiment; (F) Training curve in the Morris water maze (MWM); (F-day6) Data from the sixth day of MWM training; (G) Percentage of time spent by the mouse in the target quadrant in the MWM; (H) Statistical analysis of the number of times the mouse traverses the target quadrant in the MWM; (I) Latency to first reach the target quadrant in the MWM; (L) Baseline freezing percentage of mice in an identical testing context; (M) Percentage of freezing time of mice during the Context phase; (N) Percentage of freezing time of mice during the Cue phase. Tab Fig 3: (D–F, H) MWM tests in mice; Wildtype+AAV-GFP, n = 20; Wildtype+AAV-Gnb5-GFP, n = 23; 5xFAD + AAV-GFP, n = 23; 5xFAD + AAV-Gnb5-GFP, n = 26; (D) Training curve in the MWM; (D-day6) Data from the sixth day of MWM training; (E) Percentage of time spent in the target quadrant in the MWM; (F) Statistical analysis of the number of entries in the target quadrant in the MWM; (H) Movement speed of mice in the MWM; (I–K) The contextual fear conditioning test in mice; 5xFAD + AAV-GFP, n = 23; 5xFAD + AAV-Gnb5-GFP, n = 26; (I) Baseline freezing percentage of mice in an identical testing context; (J) Percentage of freezing time of mice during the Context phase; (K) Percentage of freezing time of mice during the Cue phase; (L) Total distance traveled in the open field test; (M) Percentage of time spent in the center area during the open field test. Tab Fig 4: (B, C) Quantification of Aβ plaques in the hippocampus sections from Wildtype and 5xFAD mice injected with either AAV-Gnb5 or AAV-GFP; Wildtype+AAV-GFP, n = 4; Wildtype+AAV-Gnb5-GFP, n = 4; 5xFAD + AAV-GFP, n = 4; 5xFAD + AAV-Gnb5-GFP, n = 4; (B) Quantification of Aβ plaques number; (C) Quantification of Aβ plaques size; (F, G) Quantification of Aβ pylaques from indicted mice lines; WT&Gnb5F/F&CamKIIa-CreERT+Vehicle, n = 4; 5xFAD&Gnb5F/F&CamKIIa-CreERT+Vehicle, n = 4; 5xFAD&Gnb5F/F&CamKIIa-CreERT+Tamoxifen, n = 4; (F) Quantification of Aβ plaque size; (G) Quantification of Aβ plaque number. Tab Fig 5: (B) Overexpression of Gnb5-AAV in 5xFAD mice affects the expression of proteins related to APP cleavage (BACE1, β-CTF, Nicastrin and APP); Statistical analysis of protein levels; n = 4, respectively; (D) Tamoxifen-induced Gnb5 knockdown in 5xFAD mice affects APP-cleaving proteins; Statistical analysis of protein levels; n = 4, respectively; (F) Gnb5-CCKO mice show altered expression of APP-cleaving proteins; Statistical analysis of protein levels; n = 6, respectively. Tab Fig 7: (C, D) Quantification of Aβ plaques in the overexpressed full-length Gnb5, truncated fragments, and mutant truncated fragment AAV in 5xFAD mice; n = 4, respectively; (C) Quantification of Aβ plaques size; (D) Quantification of Aβ plaques number; (F) Effect of overexpressing full-length Gnb5, truncated fragments, and mutant truncated fragment viruses on the expression of proteins related to APP cleavage process in 5xFAD; Statistical analysis of protein levels; n = 3, respectively.
(XLSX)