Behavioral characterization of olfactory, auditory, and motor deficits in 5×FAD mice

Importance:The 5FAD transgenic mouse model is widely used in Alzheimer's disease (AD) research due to the early onset and robustness of its AD pathology and cognitive impairment.However, motor and sensory dysfunctions in AD animal models remain less well characterized than cognitive and affective phenotypes.Objective: To characterize age-related motor, olfactory, and auditory changes in 5FAD mice and assess associated AD pathologies and neuroinflammation in relevant brain regions.Methods: 5FAD and control mice were tested at 3, 6, and 12 months.Locomotor activity and motor coordination were assessed using the open field and rotarod tests, respectively.Olfactory and auditory performance were evaluated using the buried food test and the acoustic startle response test, respectively.Amyloid- pathology and glial activation were examined in relevant nervous system components using western blot and immunohistochemistry analyses.Results: Open field measures did not differ between groups.In contrast, 5FAD mice showed an age-dependent increase in passive clinging time on the rotarod.5FAD mice also exhibited progressive age-related impairments in olfactory performance and reduced acoustic startle responsiveness.Pathological analyses revealed age-dependent increases in amyloid- accumulation and glial activation in the olfactory bulb and auditory cortex. Conclusions and Relevance:This study provides an age-related behavioral and pathological characterization of olfactory and auditory impairments in the 5FAD mouse model, with motor measures included as complementary assessments.Our findings broaden the spectrum of functional deficits associated with the AD pathology in this model.