PDF(Pubmed)
Abstract：
The majority of patients with Parkinson disease (PD) experience a loss in their sense of smell and accumulate insoluble α-synuclein aggregates in their olfactory bulbs (OB). Subjects affected by a SARS-CoV-2-linked illness (COVID-19) also frequently experience hyposmia. We previously postulated that microglial activation as well as α-synuclein and tau misprocessing can occur during host responses following microbial encounters. Using semiquantitative measurements of immunohistochemical signals, we examined OB and olfactory tract specimens collected serially at autopsies between 2020 and 2023. Deceased subjects comprised 50 adults, which included COVID19 + patients (n = 22), individuals with Lewy body disease (e.g., PD; dementia with Lewy bodies (n = 6)), Alzheimer disease (AD; n = 3), and other neurodegenerative disorders (e.g., progressive supranuclear palsy (n = 2); multisystem atrophy (n = 1)). Further, we included neurologically healthy controls (n = 9), and added subjects with an inflammation-rich brain disorder as neurological controls (NCO; n = 7). When probing for microglial and histiocytic reactivity in the anterior olfactory nuclei (AON) by anti-CD68 immunostaining, scores were consistently elevated in NCO and AD cases. In contrast, microglial signals on average were not significantly altered in COVID19 + patients relative to healthy controls, although anti-CD68 reactivity in their OB and tracts declined with progression in age. Mild-to-moderate increases in phospho-α-synuclein and phospho-tau signals were detected in the AON of tauopathy- and synucleinopathy-afflicted brains, respectively, consistent with mixed pathology, as described by others. Lastly, when both sides were available for comparison in our case series, we saw no asymmetry in the degree of pathology of the left versus right OB and tracts. We concluded from our autopsy series that after a fatal course of COVID-19, microscopic changes in the rostral, intracranial portion of the olfactory circuitry -when present- reflected neurodegenerative processes seen elsewhere in the brain. In general, microglial reactivity correlated best with the degree of Alzheimer\'s-linked tauopathy and declined with progression of age in COVID19 + patients.
摘要：
大多数帕金森病（PD）患者的嗅觉丧失，并在嗅球（OB）中积累不溶性α-突触核蛋白聚集体。受SARS-CoV-2相关疾病(COVID-19)影响的受试者也经常出现食子不振。我们先前推测小胶质细胞激活以及α-突触核蛋白和tau错误处理可能在微生物遭遇后的宿主反应期间发生。使用免疫组织化学信号的半定量测量，我们检查了在2020年至2023年之间的尸检中连续收集的OB和嗅道标本。死者包括50名成年人，其中包括COVID19+患者（n=22），患有路易体疾病的个体(例如，PD；路易体痴呆（n=6），阿尔茨海默病（AD；n=3），和其他神经退行性疾病(例如，进行性核上性麻痹（n=2）；多系统萎缩（n=1））。Further,我们包括神经健康对照（n=9），并添加患有富含炎症的脑部疾病的受试者作为神经对照(NCO;n=7)。当通过抗CD68免疫染色探测前嗅核（AON）中的小胶质细胞和组织细胞反应时，NCO和AD病例的评分持续升高.相比之下,与健康对照组相比，COVID19+患者的小胶质细胞信号平均没有显著改变，尽管其OB和束中的抗CD68反应性随着年龄的增长而下降。在受Tau病和突触核蛋白病折磨的大脑的AON中检测到磷酸-α-突触核蛋白和磷酸-tau信号的轻度至中度增加，分别,符合混合病理，正如其他人所描述的。最后,当双方都可以在我们的案例系列中进行比较时，我们在左侧和右侧OB和束的病理程度上没有看到不对称。我们从尸检系列中得出的结论是，在COVID-19的致命过程中，头颅的微观变化，嗅觉回路的颅内部分-当存在时-反映了大脑其他部位的神经退行性过程。总的来说,在COVID19+患者中,小胶质细胞反应性与阿尔茨海默病相关tau蛋白病的程度相关性最好,并随年龄的进展而下降。
