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

The 5×FAD transgenic mouse model is widely used in Alzheimer's disease (AD) research, yet its non-cognitive phenotypes -- particularly motor coordination, olfactory sensitivity, and auditory reactivity -- remain poorly characterized across the full disease trajectory. Defining these sensory and sensorimotor deficits may enhance the translational relevance of this model and provide insight into non-cognitive features in preclinical AD studies.

To characterize age-related motor, olfactory, and auditory changes in 5×FAD mice and assess associated AD pathologies and neuroinflammation in relevant brain regions.

5×FAD 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-β pathology and glial activation were examined in relevant nervous system components using western blot and immunohistochemistry analyses.

5×FAD mice showed no differences in open-field locomotion at any age, but exhibited a significantly greater passive clinging duration at 12 months compared to wild-type controls (p < 0.001). In the buried food test, olfactory latency was significantly prolonged in 5×FAD mice at 6 months (p = 0.035) and 12 months (p < 0.001). Acoustic startle amplitude was significantly reduced at 6 months (p = 0.030) and 12 months (p = 0.007). Amyloid-β and p-Tau accumulation and glial activation were elevated in the olfactory bulb and auditory cortex in an age-dependent manner.

This study provides an age-related behavioral and pathological characterization of olfactory and auditory impairments in the 5×FAD 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.