Wuhan Institute for Neuroscience and Neuroengineering, South-Central Minzu University, Wuhan, Hubei, China; The College of Life Sciences, South-Central Minzu University, Wuhan, Hubei, China.
Tongji University School of Medicine, Shanghai, China.
J Chem Neuroanat. 2022 Sep;123:102105. doi: 10.1016/j.jchemneu.2022.102105. Epub 2022 May 11.
The autonomic dysfunctions in Alzheimer's disease (AD) have been identified from many clinical studies, however, there is still a lack of evidence directly verifying the structural abnormalities of the autonomic nervous system in AD. Human medulla oblongatas from four AD patients or five non-AD subjects were obtained and observed by using immunohistochemical staining of hyperphosphorylated tau and Aβ amyloid, and post-mortem tracing techniques. We found distinct axonal and somatic immunoreactivities for the tau markers AT8 and Tau-5 in the different areas of the medulla oblongata in AD patients, which was particularly obvious in the dorsal nucleus of the vagus nerve, the nucleus of the solitary tract and the reticular nucleus. The swollen axons, which are a typical feature of axonopathy, were not only identified in the axons with immunohistochemical labeling of AT8 and Tau-5 in the different nuclei of the medulla oblongata, but also in the tracer-labeled afferent and efferent fibres of the vagus nerve in AD patients. Such changes in tauopathy and axonopathy were only occasionally found in the non-AD aged subjects. Interestingly, we did not observe any intra- or extracellular Aβ deposits in the medulla oblongatas of the AD patients or of the non-AD subjects. These results in small samples suggest that occurrence of tauopathy and axonopathy in the parasympathetic nuclei of the medulla oblongata in AD patients may implicate the change of autonomic nervous function.
阿尔茨海默病(AD)的自主神经功能障碍已在许多临床研究中得到证实,但仍缺乏直接证实 AD 患者自主神经系统结构异常的证据。我们从 4 名 AD 患者和 5 名非 AD 患者的延髓中获取样本,通过对磷酸化 tau 和 Aβ 淀粉样蛋白的免疫组织化学染色和死后示踪技术进行观察。我们发现 AD 患者延髓的不同区域存在 tau 标志物 AT8 和 Tau-5 的明显轴突和体免疫反应性,在迷走神经背核、孤束核和网状核中尤为明显。肿胀的轴突是轴突病的典型特征,不仅在 AT8 和 Tau-5 免疫组织化学标记的不同核内的轴突中被识别,而且在 AD 患者的迷走神经传入和传出纤维中也被识别。这种 tau 病和轴突病的变化在非 AD 老年患者中偶尔发现。有趣的是,我们在 AD 患者或非 AD 患者的延髓中均未观察到任何细胞内或细胞外的 Aβ 沉积。这些小样本的结果表明,AD 患者延髓副交感神经核中 tau 病和轴突病的发生可能暗示自主神经功能的改变。