Differences in hearing across the lifespan in two strains of Alzheimer's mouse models as measured using behavioral and physiological techniques.

Abstract

Alzheimer's disease (AD) is a brain condition with heterogeneity in disease progression due to genetic and environmental variables. There is a critical need to better understand the relationship of AD pathologies and potential modifiable factors like hearing loss. Auditory processing measurements in AD mouse models have been reported, but the results are mixed. Most were conducted using evoked potential recordings measured under anesthesia, unlike typical hearing assessments on aging adult humans. Here, we used operant conditioning and signal detection theory to measure daily pure tone behavioral detection throughout the lifespan of trained mutant and wild-type (WT) control APP/PS1 (on a C57BL/6J background) and 5xFAD (on a C57/SJL background) mice. At the conclusion of operant testing, auditory brainstem response (ABR) measures were taken on the same subjects to determine if evoked potentials provided accurate estimates of perceptual abilities. Behavioral detection worsened significantly across the lifespan in APP/PS1 mice, but there were no differences between mutant and WT mice. For 5xFAD mice, behavioral thresholds generally worsened over the lifespan but with substantial variability, which may be explained by genetic heterogeneity among the background strain. There were no differences between 5xFAD mutant and WT mice. ABR hearing threshold estimates generally matched behavioral findings, with APP/PS1 having significantly worse thresholds than 5xFAD mice but no within-model differences between mutants and WTs. The within-subject differences between behavioral and ABR thresholds ranged from <1 dB to over 40 dB across subjects, suggesting physiological measurements of auditory function are not necessarily reflective of an animal's acoustic perception.