Alzheimer's Disease: What Can We Learn From the Peripheral Olfactory System?

The sense of smell has been shown to deteriorate in patients with some neurodegenerative disorders. In Parkinson's disease (PD) and Alzheimer's disease (AD), decreased ability to smell is associated with early disease stages. Thus, olfactory neurons in the nose and olfactory bulb (OB) may provide a window into brain physiology and pathophysiology to address the pathogenesis of neurodegenerative diseases. Because nasal olfactory receptor neurons regenerate throughout life, the olfactory system offers a broad variety of cellular mechanisms that could be altered in AD, including odorant receptor expression, neurogenesis and neurodegeneration in the olfactory epithelium, axonal targeting to the OB, and synaptogenesis and neurogenesis in the OB. This review focuses on pathophysiological changes in the periphery of the olfactory system during the progression of AD in mice, highlighting how the olfactory epithelium and the OB are particularly sensitive to changes in proteins and enzymes involved in AD pathogenesis. Evidence reviewed here in the context of the emergence of other typical pathological changes in AD suggests that olfactory impairments could be used to understand the molecular mechanisms involved in the early phases of the pathology.

在患有某些神经退行性疾病的患者中，嗅觉已被证明会退化。在帕金森病（PD）和阿尔茨海默病（AD）中，嗅觉能力下降与疾病早期阶段有关。因此，鼻子中的嗅觉神经元和嗅球（OB）可能为了解大脑生理学和病理生理学提供一个窗口，以解决神经退行性疾病的发病机制。由于鼻腔嗅觉受体神经元在一生中都能再生，嗅觉系统提供了多种在AD中可能发生改变的细胞机制，包括气味受体表达、嗅上皮中的神经发生和神经退行性变、轴突靶向嗅球以及嗅球中的突触发生和神经发生。这篇综述重点关注小鼠阿尔茨海默病进展过程中嗅觉系统外周的病理生理变化，强调嗅上皮和嗅球如何对参与阿尔茨海默病发病机制的蛋白质和酶的变化特别敏感。在此结合阿尔茨海默病其他典型病理变化出现的情况所综述的证据表明，嗅觉损伤可用于了解该病理早期阶段所涉及的分子机制。