Auditory brainstem response deficits precede and are associated with subsequent auditory cortical amyloid burden in male APP/PS1 mice

Background Auditory dysfunction is considered one of the early manifestations of Alzheimer's disease (AD). However, its evolutionary characteristics with the progression of AD have not been fully studied, and the temporal relationship between this sensory impairment and the typical pathology of the disease is unclear. Objective To investigate whether auditory dysfunction precedes auditory cortical amyloid-β (Aβ) deposition during AD progression. Methods This study longitudinally assessed the threshold and amplitude of auditory brainstem response (ABR) in male APP/PS1 mice and male wild-type littermate mice at different ages, and quantitatively analyzed Aβ plaques in the auditory cortex of APP/PS1 mice using immunofluorescence. Further evaluation was conducted on the correlation between early ABR indicators and subsequent Aβ burden. A multivariate logistic regression model was constructed based on ABR features to distinguish APP/PS1 mice from wild-type controls in the pre-plaque stage. Results APP/PS1 mice exhibited progressive hearing impairment, with auditory impairment emerging at 8–12 weeks of age and detectable Aβ deposition appearing at 20 weeks of age. Early ABR abnormalities were significantly correlated with subsequent Aβ burden. Furthermore, a multivariable logistic regression model based on ABR threshold and the amplitudes of waves I, III, and IV showed good discriminatory performance for distinguishing APP/PS1 mice from wild-type controls during the pre-plaque stage. Conclusions ABR abnormalities occur before detectable cortical plaque deposition in APP/PS1 mice and are associated with subsequent auditory cortical Aβ burden. These findings suggest that ABR-based features may serve as candidate non-invasive functional indicators for assessing early pathological progression of AD.