Longitudinal investigation of spatial memory and retinal parameters in a 5xFAD model of Alzheimer’s disease reveals differences dependent on genotype and sex

The retinal phenotype of Alzheimer's disease (AD), its connection to spatial memory, and the influence of sex on the phenotype are poorly understood. Here, we investigate the retina and spatial memory of 5xFAD mouse models of AD by measuring retinal and behavioral parameters. A custom-built optical coherence tomography (OCT) system is used to image the retina of 32 transgenic and 32 non-transgenic 5xFAD mice over the course of 6 months (3-9 months of age). The Morris water maze (MWM) test was performed to examine correlations between the retinal and spatial memory phenotype of the mouse model. Total retinal and inner retinal layer thickness increased slightly over the measurement period, while outer retinal layer and retinal nerve fiber layer thickness showed no significant change. The correlation analysis between MWM and layer thickness data revealed a positive correlation between inner nuclear layer thickness and spatial memory capabilities. OCT and MWM data revealed sex-based differences in the retinal phenotype of the 5xFAD mouse model, with changes in retinal thickness in different stages of the study and dissimilar correlations between retinal and spatial memory phenotype.