Characterization and comparison of memory and affective behavior in common transgenic mouse models of Alzheimer’s disease

Abstract

AbstractBackgroundAlzheimer’s disease (AD) is a neurodegenerative disorder with cognitive decline, yet over 90% of patients also develop behavioral symptoms during disease progression. While a few studies have identified some aberrant behaviors in transgenic mouse models of AD, rigorous characterization and comparison of AD models for memory and affective behavior has yet to be done.MethodsWe characterized memory and affective behavior in three commonly AD mouse models (5xFAD, APP/PS1, and APPNLGF mice) at 10 months of age. We evaluated working, spatial, and social memory deficits using Y‐maze, novel object recognition (NOR), social recognition, and Morris water maze (MWM). We assayed affective behavior with open field, light‐dark box, social interaction and tail suspension tests. Then, we evaluated the dynamic changes in memory and affective behavior in 5xFAD mice at 6 and 10 months of age.ResultsAll three AD mouse lines demonstrated deficits in working, spatial and social memory compared to WT mice. However, 5XFAD and APPNLGF mice showed more severe working and social memory deficits compared to APP/PS1 mice. In the open field, 5xFAD but not APPNLGF and APP/PS1 mice showed a reduction in the time spent and the number of entries in the center of the arena. In the light/dark box test, both 5xFAD and APPNLGF but not APP/PS1 mice entered land spent less time in the light compartment. Similarly, 5xFAD and APPNLGF mice demonstrated reduced time spent and number of entries around the conspecific in the social interaction test. Finally, 5xFAD and APPNLGF but not APP/PS1 mice had increased immobility in the tail‐suspension test. Interestingly, changes in the affective behavior but not memory deficits were found in 5XFAD mice at 6 months of age, and some of these behavioral alterations worsened at 10 months of age.ConclusionsAlthough 10‐month‐old 5xFAD, APPNLGF, and APP/PS1 mice displayed working, spatial and social memory deficits, only 5xFAD and APPNLGF showed robust anxiety‐ and depressive‐like behaviors at this time point. Importantly, the 5xFAD mice displayed significant deficits in affective behavior but not memory impairment at an early time‐point, suggesting that the AD‐pathology may drive changes in affective behavior before more overt memory deficits.