In animal models, brain neurodegeneration biomarkers drain into cervical lymph nodes (CLNs), and this drainage function is reduced with ageing. If this occurred in humans, CLNs may provide a readily accessible measure of this aspect of protein clearance. We tested this hypothesis in people using ultrasound-guided fine needle aspiration (FNA). We measured amyloid-beta 40 and 42, phospho-Tau-181, glial-fibrillary-acidic-protein, and neurofilament-light using single molecule array in CLN aspirates and plasma from: i) a discovery cohort of 25 autoimmune patients, and from ii) plasma, CLNs and capillary blood in four healthy volunteers, an optimisation cohort. FNA was well-tolerated by all participants. In both cohorts, all biomarkers were detected in all plasma and CLN samples, other than neurofilament-light (8/17 of discovery cohort). CLN biomarker concentrations were significantly greater than plasma concentrations for all except neurofilament-light, most markedly for phospho-Tau-181 (266-fold; P<0.02), whose CLN concentrations decreased with age (Spearman r=-0.66, P=0.001). This study presents the first evidence that neurodegenerative biomarkers are detectable in human CLNs. Raised CLN:plasma biomarker ratios suggest their concentration in CLNs may offer a distinct compartment for minimally-invasive measurement of brain clearance and lymphatic drainage, with potential applicability to study of ageing and future clinical trials.

中文翻译：

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神经退行性液体生物标志物富含人类颈部淋巴结


在动物模型中，脑神经退行性生物标志物排入颈部淋巴结 （CLN），这种引流功能会随着年龄的增长而降低。如果这发生在人类中，CLN 可能提供一种易于获得的蛋白质清除率方面的测量方法。我们在使用超声引导下细针穿刺 （FNA） 的人群中检验了这一假设。我们使用单分子阵列测量了 CLN 抽吸物和血浆中的淀粉样蛋白-β 40 和 42、磷酸化 Tau-181、神经胶质纤维酸性蛋白和神经丝-光：i） 25 名自身免疫患者的发现队列，以及 ii） 四名健康志愿者的血浆、CLN 和毛细血管血，一个优化队列。所有参与者对 FNA 的耐受性良好。在这两个队列中，除神经丝光外，在所有血浆和 CLN 样本中检测到所有生物标志物 （发现队列的 8/17）。除神经丝光外，所有 CLN 生物标志物浓度均显著高于血浆浓度，磷酸化 Tau-181 最明显（266 倍;P<0.02），其 CLN 浓度随年龄增长而降低 （Spearman r=-0.66，P=0.001）。本研究提供了在人类 CLN 中可检测到神经退行性生物标志物的第一个证据。升高的 CLN：血浆生物标志物比率表明它们在 CLN 中的浓度可能为脑清除和淋巴引流的微创测量提供了一个独特的隔间，可能适用于衰老研究和未来的临床试验。