To investigate Aβ plaque accumulation, immunofluorescence staining was conducted as previously described (28 (link)). Serial sections from the prefrontal cortex (PFC; bregma, 1.94–1.42 mm) to the hippocampus (bregma, − 1.70 to − 2.18 mm) were used for immunofluorescent staining. Three sections per animal were blocked with 5% normal goat serum (Vector Laboratories) and then immersed in anti-mouse 6E10 primary antibody (BioLegend) overnight at 4 °C. Sections were immersed in Alexa Fluor conjugated secondary antibody (Invitrogen) for 90 minutes, and incubated in 4′-6-diamidino-2-phenylindole solution (Sigma-Aldrich) for 10 minutes to stain the cellular nuclei. Stained sections were imaged using a fluorescence microscope (Olympus, Japan), and Aβ plaque load in the hippocampal subregions (CA1: cornu ammonis 1 and DG: dentate gyrus) and PFC (PL: prelimbic cortex and IL: infralimbic cortex) was quantified using Image J software (NIH). For Aβ plaque load analysis, the number of 6E10-positive pixels was divided by the number of whole pixels in each image and, according to previous reports (18 (link),29 (link)), the data are reported as the percentage area occupied by the 6E10-positive signal. To apply the same selection criteria to all cuts, a template was created from a region of interest in the hippocampus and PFC and applied on each sample.