雄性APP/PS1小鼠中听觉脑干反应缺陷先于并与其后听觉皮层淀粉样蛋白负荷相关

文献信息

中文摘要

背景： 听觉功能障碍被认为是阿尔茨海默病（AD）的早期表现之一。然而，其随AD进展的演变特征尚未得到充分研究，且这种感觉障碍与疾病典型病理之间的时间关系尚不清楚。目的：探讨在AD进展过程中听觉功能障碍是否先于听觉皮层淀粉样蛋白-β（Aβ）沉积。方法：本研究纵向评估了不同年龄雄性APP/PS1小鼠和雄性野生型同窝小鼠的听觉脑干反应（ABR）阈值和波幅，并使用免疫荧光定量分析APP/PS1小鼠听觉皮层中的Aβ斑块。进一步评估了早期ABR指标与随后Aβ负荷之间的相关性。基于ABR特征构建多因素logistic回归模型，以在斑块前期区分APP/PS1小鼠与野生型对照。结果：APP/PS1小鼠表现出进行性听力损害，听觉损害在8-12周龄出现，可检测到的Aβ沉积在20周龄出现。早期ABR异常与随后的Aβ负荷显著相关。此外，基于ABR阈值以及波I、III和IV波幅的多变量logistic回归模型在斑块前期区分APP/PS1小鼠与野生型对照方面显示出良好的判别性能。结论：在APP/PS1小鼠中，ABR异常发生在可检测到的皮层斑块沉积之前，并与随后的听觉皮层Aβ负荷相关。这些发现表明，基于ABR的特征可能作为评估AD早期病理进展的候选无创功能指标。

英文摘要

BackgroundAuditory 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.ObjectiveTo investigate whether auditory dysfunction precedes auditory cortical amyloid-β (Aβ) deposition during AD progression.MethodsThis 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.ResultsAPP/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.ConclusionsABR 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.