Fig. 1: Brain networks, AD-like pathology and study overview.

a A 172 ROIs-atlas is used to generate the connectomes. Color-coded subdivision in the three networks of the triple network model: default-mode network (DMN) in green, salience network (SN) in pink, lateral-cortical network (LCN) in orange; regions in common across all three networks (light blue), regions shared by DMN and LCN (light purple) are also shown. b Example of average connectomes shown (2 regions removed from the connectomes images—but kept for all analyses—solely for visualization purposes, i.e. smaller than 10 voxels). c AD-like pathology trajectory illustrated on the timeline in warm colors [28, 29, 31]: β-amyloid accumulation (yellow), synapse loss (orange) and phosphorylated-tau accumulation (red). Decreasing performance on memory tests (e.g., Y- maze test) [28] in blue. Imaging timepoints (MRI, orange) indicated by black dotted arrows. A month before the first imaging timepoint (in each group, Supplementary Table 1), all mice undergo a minimally invasive surgical procedure [37] where a head-plate (HP) is affixed to the skull to reduce susceptibility artifacts and motion (yellow). The treatment (Tx) period is indicated on the timeline (purple). Average Z-scored connectomes/group/timepoint are shown above the timeline. Data from WT mice are outlined in grey (lower left). Data from AD (and AD_vehicle/AD_veh) groups are outlined in black (upper right). Data from the AD_Tx group (at 22 M) are outlined in purple. The number of mice (‘N’) and runs (‘n’) indicated above each connectome. ROIs: regions of interest. Animal breakdown: 4 M: N_WT = 5/5 M/F; N_AD = 7/8 M/F; 6 M: N_WT = 5/5 M/F; N_AD = 5/7 M/F; 9 M: N_WT = 6/4 M/F; N_AD = 6/5 M/F; 20 M: N_WT = 5/3 M/F; N_AD = 12/7 M/F; 22 M: N_WT = 5/0 M/F; N_ADveh = 6/3 M/F; N_ADTx = 5/4 M/F.