Kaylegian Katherine, Stebritz Amanda J, Weible Aldis P, Wehr Michael
Department of Psychology, Institute of Neuroscience, University of Oregon, Eugene, OR, United States.
Front Aging Neurosci. 2019 Apr 2;11:66. doi: 10.3389/fnagi.2019.00066. eCollection 2019.
Alzheimer's patients show auditory temporal processing deficits very early in disease progression, before the onset of major cognitive impairments. In addition to potentially contributing to speech perception and communication deficits in patients, this also represents a potential early biomarker for Alzheimer's. For this reason, tests of temporal processing such as gap detection have been proposed as an early diagnosis tool. For a biomarker such as gap detection deficits to have maximum clinical value, it is important to understand what underlying neuropathology it reflects. For example, temporal processing deficits could arise from alterations at cortical, midbrain, or brainstem levels. Mouse models of Alzheimer's disease can provide the ability to reveal in detail the molecular and circuit pathology underlying disease symptoms. Here we tested whether 5XFAD mice, a leading Alzheimer's mouse model, exhibit impaired temporal processing. We found that 5XFAD mice showed robust gap detection deficits. Gap detection deficits were first detectable at about 2 months of age and became progressively worse, especially for males and for longer gap durations. We conclude that 5XFAD mice are well-suited to serve as a model for understanding the circuit mechanisms that contribute to Alzheimer's-related gap detection deficits.
阿尔茨海默病患者在疾病进展的早期，即在出现主要认知障碍之前，就表现出听觉时间处理缺陷。除了可能导致患者的言语感知和交流缺陷外，这也代表了阿尔茨海默病的一种潜在早期生物标志物。因此，诸如间隙检测等时间处理测试已被提议作为一种早期诊断工具。对于像间隙检测缺陷这样的生物标志物要具有最大的临床价值，了解它所反映的潜在神经病理学是很重要的。例如，时间处理缺陷可能源于皮层、中脑或脑干水平的改变。阿尔茨海默病的小鼠模型能够详细揭示疾病症状背后的分子和回路病理学。在这里，我们测试了阿尔茨海默病主要小鼠模型5XFAD小鼠是否表现出时间处理受损。我们发现5XFAD小鼠表现出明显的间隙检测缺陷。间隙检测缺陷在大约2个月大时首次可检测到，并且逐渐恶化，尤其是雄性小鼠以及间隙持续时间更长的情况。我们得出结论，5XFAD小鼠非常适合作为理解导致阿尔茨海默病相关间隙检测缺陷的回路机制的模型。
