Early detection will be crucial for effective treatment or prevention of Alzheimer's disease. The identification and validation of early, noninvasive biomarkers is therefore key to avoiding the most devastating aspects of Alzheimer's disease. Measures of central auditory processing such as gap detection have recently emerged as potential biomarkers in both human patients and the 5XFAD mouse model of Alzheimer's disease. Full validation of gap detection deficits as a biomarker will require detailed understanding of the underlying neuropathology, including which brain structures are involved and how the operation of neural circuits is affected. Here we show that 5XFAD mice exhibit gap detection deficits as early as 2 months of age, well before development of Alzheimer's disease-associated pathology. We then examined responses of neurons in the auditory cortex to gaps in white noise. Both gap responses and baseline firing rates were robustly and progressively degraded in 5XFAD mice compared to littermate controls. These impairments were first evident at 2-4 months of age in males, and 4-6 months in females. This demonstrates early-onset impairments to the central auditory system, which could be due to damage in the auditory cortex, upstream subcortical structures, or both.

中文翻译：

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5XFAD 小鼠在听觉皮层中表现出早发间隙编码缺陷。

早期发现对于有效治疗或预防阿尔茨海默病至关重要。因此，早期非侵入性生物标志物的识别和验证是避免阿尔茨海默病最具破坏性方面的关键。诸如间隙检测之类的中央听觉处理措施最近已成为人类患者和阿尔茨海默病 5XFAD 小鼠模型的潜在生物标志物。作为生物标志物的间隙检测缺陷的全面验证将需要详细了解潜在的神经病理学，包括涉及哪些大脑结构以及神经回路的运行如何受到影响。在这里，我们表明 5XFAD 小鼠早在 2 个月大时就表现出间隙检测缺陷，远早于阿尔茨海默病相关病理学的发展。然后我们检查了听觉皮层中的神经元对白噪声间隙的反应。与同窝对照相比，5XFAD 小鼠的间隙响应和基线放电率均显着且逐渐降低。这些损害首先在雄性 2-4 个月大时和雌性 4-6 个月大时出现。这表明中枢听觉系统的早发性损伤可能是由于听觉皮层、上游皮层下结构或两者的损伤造成的。