Fig. 7.

GGA3 deletion increases levels of Aβ42 and amyloid plaques increase in the hippocampus of old 5XFAD;GGA3KO mice at 12 months of age. a-b Levels of human Aβ42 were quantified by ELISA (ng/mg of total protein) (Invitrogen) in hippocampus (a) and cortex (b) GuHCl extracts from 12 months old GGA3WT;5XFAD, GGA3Het;5XFAD and GGA3KO;5XFAD male and female mice. GGA3 deletion resulted in increased Aβ42 levels in the hippocampus of both male and female 12 months old 5XFAD mice. GGA3KO;5XFAD mice also had a trend of increased Aβ42 levels in the cortex at 12 months of age. One-way ANOVA with Fisher’s LSD post hoc tests was applied to each genotype group. * p < 0.05, ** < 0.01, *** p < 0.001. c-d Coronal brain sections from 12 months old GGA3WT;5XFAD and GGA3KO;5XFAD male and female mice were stained with Thioflavin-S. Representative images show amyloid plaques from 12 months old female GGA3WT;5XFAD (c) and GGA3KO;5XFAD mice (d). Increased Thioflavin-S positive amyloid plaques were frequently observed in the area of dentate gyrus (DG), stratum lucidum (slu), and CA1 stratum oriens (CA1so) at 12 months of age (d). Scale bar is 500 μm. e-h The graphs represent the quantification of Thioflavin-S positive plaques in hippocampus (e) and cortex (f) of GGA3WT;5XFAD and GGA3KO;5XFAD male and female mice. GGA3KO;5XFAD female mice have significantly increased amyloid plaque burden in hippocampus, but not in cortex, compared to GGA3WT;5XFAD females at 12 months of age. GGA3KO;5XFAD male mice also show a similar trend when compared to GGA3WT;5XFAD males. g-h The graphs show average size of amyloid plaques (μm²) and number of amyloid plaques in hippocampus and cortex of GGA3WT;5XFAD and GGA3KO;5XFAD mice. A significantly increase in size of amyloid plaques but not number of amyloid plaques was found in hippocampus of GGA3KO;5XFAD females. Total number of mice in each group is indicated within bars. All graphs represent mean ± SEM. Unpaired t-test with Welch’s correction was performed. * p < 0.05, ** p < 0.01, *** p < 0.001