Department of Neurosciences, Biomedicine, and Movement Sciences, Policlinico G. B. Rossi, University of Verona, 37134, Verona, Italy.
Neurology Unit, Department of Medicine, Surgery and Health Sciences, Ospedale Cattinara, University of Trieste, 34128, Trieste, Italy.
Transl Neurodegener. 2022 Jul 28;11(1):37. doi: 10.1186/s40035-022-00311-3.
In patients with Parkinson's disease (PD), real-time quaking-induced conversion (RT-QuIC) detection of pathological α-synuclein (α-syn) in olfactory mucosa (OM) is not as accurate as in other α-synucleinopathies. It is unknown whether these variable results might be related to a different distribution of pathological α-syn in OM. Thus, we investigated whether nasal swab (NS) performed in areas with a different coverage by olfactory neuroepithelium, such as agger nasi (AN) and middle turbinate (MT), might affect the detection of pathological α-syn.
NS was performed in 66 patients with PD and 29 non-PD between September 2018 and April 2021. In 43 patients, cerebrospinal fluid (CSF) was also obtained and all samples were analyzed by RT-QuIC for α-syn.
In the first round, 72 OM samples were collected by NS, from AN (NS) or from MT (NS), and 35 resulted positive for α-syn RT-QuIC, including 27/32 (84%) from AN, 5/11 (45%) from MT, and 3/29 (10%) belonging to the non-PD patients. Furthermore, 23 additional PD patients underwent NS at both AN and MT, and RT-QuIC revealed α-syn positive in 18/23 (78%) NS samples and in 10/23 (44%) NS samples. Immunocytochemistry of NS preparations showed a higher representation of olfactory neural cells in NS compared to NS. We also observed α-syn and phospho-α-syn deposits in NS from PD patients but not in controls. Finally, RT-QuIC was positive in 22/24 CSF samples from PD patients (92%) and in 1/19 non-PD.
In PD patients, RT-QuIC sensitivity is significantly increased (from 45% to 84%) when NS is performed at AN, indicating that α-syn aggregates are preferentially detected in olfactory areas with higher concentration of olfactory neurons. Although RT-QuIC analysis of CSF showed a higher diagnostic accuracy compared to NS, due to the non-invasiveness, NS might be considered as an ancillary procedure for PD diagnosis.
在帕金森病（PD）患者中，实时震颤诱导转化（RT-QuIC）检测嗅黏膜（OM）中的病理性α-突触核蛋白（α-syn）的准确性不如其他α-突触核蛋白病。目前尚不清楚这些不同的结果是否与 OM 中病理性α-syn 的不同分布有关。因此，我们研究了在嗅上皮细胞不同覆盖区域进行鼻拭子（NS）检查，例如额窦（AN）和中鼻甲（MT），是否会影响病理性α-syn 的检测。
2018 年 9 月至 2021 年 4 月，我们对 66 名 PD 患者和 29 名非 PD 患者进行了 NS 检查。在 43 名患者中，还获得了脑脊液（CSF），并通过 RT-QuIC 对所有样本进行了α-syn 分析。
在第一轮中，我们通过 NS 从 AN（NS）或 MT（NS）采集了 72 个 OM 样本，其中 35 个样本的α-syn RT-QuIC 结果为阳性，包括 27/32（84%）来自 AN，5/11（45%）来自 MT，3/29（10%）来自非 PD 患者。此外，23 名额外的 PD 患者在 AN 和 MT 处均进行了 NS，RT-QuIC 显示 18/23（78%）个 NS 样本和 10/23（44%）个 NS 样本为α-syn 阳性。NS 制剂的免疫细胞化学显示 NS 中嗅神经细胞的代表性更高。我们还观察到 PD 患者的 NS 中存在α-syn 和磷酸化α-syn 沉积物，但在对照组中没有。最后，24 名 PD 患者的 22/24 份 CSF 样本（92%）和 19 名非 PD 患者中的 1/19 份 CSF 样本的 RT-QuIC 为阳性。
在 PD 患者中，当在 AN 进行 NS 时，RT-QuIC 的敏感性显著增加（从 45%增加到 84%），这表明 α-syn 聚集物优先在嗅神经元浓度较高的嗅区被检测到。尽管 CSF 的 RT-QuIC 分析与 NS 相比显示出更高的诊断准确性，但由于其非侵入性，NS 可被视为 PD 诊断的辅助程序。
