Cochlear Amyloid-β42 Accumulation Drives Progressive Auditory Neuropathy in 5XFAD Mice: A Potential Biomarker for Early Alzheimer's Disease

Background Emerging evidence suggests auditory dysfunction may serve as an early biomarker of Alzheimer’s disease (AD). This study investigates amyloid-beta 42 (Aβ42) accumulation in the cochlea and its relationship to auditory dysfunction in 5XFAD mice. Methods Immunofluorescence imaging assessed Aβ42 deposition in cochlear structures (spiral ganglion neurons [SGNs], vasculature) at 8 weeks. Auditory brainstem responses (ABR) were analyzed using multimetric methods (Wave I amplitude, signal-to-noise ratio [SNR], phase-locking precision, cross-correlation) at 8 and 16 weeks. Results Aβ42 deposition was detected in SGNs and vasculature by 8 weeks. 5XFAD mice exhibited reduced ABR Wave I amplitude (p < 0.01) and SNR versus wild-type, indicating impaired neural encoding. By 16 weeks, Wave I amplitude merged with cochlear microphonics, reflecting advanced neural deterioration. Synchrony analyses confirmed progressive auditory nerve desynchronization. Conclusion Cochlear Aβ42 accumulation correlates with progressive auditory neuropathy in AD models, highlighting its biomarker potential. Multimetric ABR reveals neural synchrony deficits precede threshold shifts, emphasizing the need for advanced auditory assessments.