Department of Neurology and Centre of Clinical Neuroscience, First Faculty of Medicine, Charles University and General University Hospital in Prague, Prague, Czech Republic.
Institute of Medical Biochemistry and Laboratory Diagnostics, First Faculty of Medicine, Charles University and General University Hospital in Prague, Prague, Czech Republic.
Mov Disord. 2022 May;37(5):983-992. doi: 10.1002/mds.28942. Epub 2022 Feb 7.
Sialic acid-protein interactions are involved in regulating central nervous system immunity; therefore, derangements in sialylation could be involved in neurodegeneration.
We evaluate the differences in serum transferrin sialylation in prodromal and early-stage Parkinson's disease (PD), its relation to substantia nigra degeneration, and the risk of phenoconversion to manifest disease.
Sixty treatment-naive PD patients; 72 polysomnography-confirmed isolated rapid eye movement sleep behavior disorder (iRBD) patients, that is, patients with prodromal synucleinopathy; and 46 healthy volunteers aged ≥45 years and drinking ≤60 standard drinks per month were included. The proportion of serum low-sialylated, carbohydrate-deficient transferrin (CDT) isoforms was assessed using high-performance liquid chromatography, and the values were adjusted for alcohol intake (CDT ). Dopamine transporter single-photon emission computed tomography (DaT-SPECT) imaging was performed. In iRBD, phenoconversion risk of DaT-SPECT and CDT was evaluated using Cox regression adjusted for age and sex.
Median CDT was lower in PD (1.1 [interquartile range: 1.0-1.3]%) compared to controls (1.2 [1.1-1.6]%) (P = 0.001). In iRBD, median CDT was lower in subjects with abnormal (1.1 [0.9-1.3]%) than normal (1.3 [1.2-1.6]%) DaT-SPECT (P = 0.005). After a median 44-month follow-up, 20% of iRBD patients progressed to a manifest disease. Although iRBD converters and nonconverters did not significantly differ in CDT levels (P = 0.189), low CDT increased the risk of phenoconversion with hazard ratio 3.2 (P = 0.045) but did not refine the phenoconversion risk associated with abnormal DaT-SPECT yielding hazard ratio 15.8 (P < 0.001).
Decreased serum CDT is associated with substantia nigra degeneration in synucleinopathies. iRBD patients with low CDT are more likely to phenoconvert to manifest disease. © 2022 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson Movement Disorder Society.
唾液酸-蛋白相互作用参与调节中枢神经系统免疫；因此，唾液酸化的异常可能与神经退行性变有关。
我们评估前驱期和早期帕金森病（PD）患者血清转铁蛋白唾液酸化的差异，及其与黑质变性的关系，以及向显性疾病表型转化的风险。
纳入 60 例未经治疗的 PD 患者；72 例经多导睡眠图证实的孤立性快速眼动睡眠行为障碍（iRBD）患者，即具有前驱性突触核蛋白病的患者；和 46 名年龄≥45 岁且每月饮酒量≤60 标准杯的健康志愿者。使用高效液相色谱法评估血清低唾液酸化、糖缺乏转铁蛋白（CDT）同工型的比例，并根据酒精摄入量进行调整（CDT）。对多巴胺转运体单光子发射计算机断层扫描（DaT-SPECT）成像进行评估。在 iRBD 中，使用 Cox 回归调整年龄和性别，评估 DaT-SPECT 和 CDT 的表型转化风险。
与对照组（1.2%[1.1%-1.6%]）相比，PD 患者的中位 CDT 较低（1.1%[1.0%-1.3%]）（P=0.001）。在 iRBD 中，与正常 DaT-SPECT（1.3%[1.2%-1.6%]）相比，异常 DaT-SPECT 的受试者的中位 CDT 更低（1.1%[0.9%-1.3%]）（P=0.005）。中位随访 44 个月后，20%的 iRBD 患者进展为显性疾病。尽管 iRBD 转化者和非转化者的 CDT 水平没有显著差异（P=0.189），但低 CDT 增加了表型转化的风险，风险比为 3.2（P=0.045），但并未改善与异常 DaT-SPECT 相关的表型转化风险，风险比为 15.8（P<0.001）。
血清 CDT 降低与突触核蛋白病的黑质变性有关。CDT 较低的 iRBD 患者更有可能向显性疾病表型转化。© 2022 作者。运动障碍由 Wiley Periodicals LLC 代表国际帕金森运动障碍学会出版。
