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

TL;DR

This study shows that amyloid-beta 42 buildup in the inner ear causes hearing issues in mice, suggesting it could be an early sign of Alzheimer’s disease.

Contribution

The study identifies cochlear Aβ42 accumulation as a novel biomarker for early Alzheimer’s disease.

Findings

Aβ42 was detected in cochlear neurons and blood vessels as early as 8 weeks in 5XFAD mice.

Multimetric ABR analysis revealed impaired neural encoding and progressive auditory nerve desynchronization.

Wave I amplitude changes indicated advanced neural deterioration by 16 weeks in 5XFAD mice.

Abstract

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.

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.

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.

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.

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