Smell and Taste Center, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.
Lancet Neurol. 2017 Jun;16(6):478-488. doi: 10.1016/S1474-4422(17)30123-0.
In patients with neurodegenerative diseases, there is a spectrum of smell dysfunction ranging from severe loss, as seen in Alzheimer's disease and Parkinson's disease, to relatively little loss, as seen in progressive supranuclear palsy. Given the ubiquitous but varying degrees of olfactory dysfunction among such diseases, it is conceivable that differential disruption of a common primordial neuropathological substrate causes these differences in olfactory function. For example, the amount of damage to forebrain neurotransmitter and neuromodulator circuits, most notably those involving cholinergic transmission, appears to be correlated with quantitative smell test scores across a wide range of neurodegenerative diseases. Thus, a key question is whether damage to such a substrate is the basis for the perceptual differences in olfaction or whether disease-specific or other entities, such as respiratory infections or pollution, are responsible. In light of the early preclinical onset of smell deficits in many neurodegenerative diseases, the answer to this question might provide crucial insight into the cause of disease pathology at its earliest stages of development.
在神经退行性疾病患者中，存在从严重损失（如阿尔茨海默病和帕金森病）到相对较小损失（如进行性核上性麻痹）的一系列嗅觉功能障碍。鉴于这些疾病中普遍存在但程度不同的嗅觉功能障碍，可以想象，共同原始神经病理底物的差异破坏导致了嗅觉功能的这些差异。例如，前脑神经递质和神经调质回路的损伤程度，特别是涉及胆碱能传递的回路，似乎与广泛的神经退行性疾病中的定量嗅觉测试评分相关。因此，一个关键问题是，这种基质的损伤是否是嗅觉感知差异的基础，或者是否是疾病特异性或其他实体（如呼吸道感染或污染）所致。鉴于许多神经退行性疾病中嗅觉缺陷的早期临床前发病，这个问题的答案可能为疾病病理学的最早发展阶段的病因提供关键的见解。
