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耳蜗β淀粉样蛋白42积累导致5XFAD小鼠进行性听觉神经病变：早期阿尔茨海默病的潜在生物标志物

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

作者信息

Al-Sallami Dheyaa, Aameri Raheem F H Al, Tischkau Shelley, Rybak Leonard P, Ramkumar Vickram

机构信息

Southern Illinois University School of Medicine.

出版信息

Res Sq. 2025 Apr 21:rs.3.rs-6431143. doi: 10.21203/rs.3.rs-6431143/v1.

DOI:10.21203/rs.3.rs-6431143/v1
PMID:40313736
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC12045352/
Abstract

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.

摘要

背景

新出现的证据表明，听觉功能障碍可能是阿尔茨海默病（AD）的早期生物标志物。本研究调查了5XFAD小鼠耳蜗中β淀粉样蛋白42（Aβ42）的积累及其与听觉功能障碍的关系。

方法

通过免疫荧光成像评估8周龄时耳蜗结构（螺旋神经节神经元[SGNs]、脉管系统）中Aβ42的沉积情况。在8周和16周时，使用多指标方法（I波振幅、信噪比[SNR]、锁相精度、互相关）分析听觉脑干反应（ABR）。

结果

到8周时，在SGNs和脉管系统中检测到Aβ42沉积。与野生型相比，5XFAD小鼠的ABR I波振幅（p < 0.01）和SNR降低，表明神经编码受损。到16周时，I波振幅与耳蜗微音器电位合并，反映出神经进一步退化。同步分析证实听觉神经同步性逐渐丧失。

结论

耳蜗Aβ42积累与AD模型中进行性听觉神经病变相关，凸显了其作为生物标志物的潜力。多指标ABR揭示神经同步性缺陷先于阈值变化，强调了进行高级听觉评估的必要性。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9680/12045352/58f915542027/nihpp-rs6431143v1-f0008.jpg
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