Cerebrospinal fluid p-tau217 performs better than p-tau181 as a biomarker of Alzheimer's disease.,Nature Communications

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Cerebrospinal fluid p-tau217 performs better than p-tau181 as a biomarker of Alzheimer's disease.
Nature Communications ( IF 14.7 ) Pub Date : 2020-04-03 , DOI: 10.1038/s41467-020-15436-0
Shorena Janelidze ₁ , Erik Stomrud ₁ , Ruben Smith _{1,

2} , Sebastian Palmqvist _{1,

2} , Niklas Mattsson _{1,

2,

3} , David C Airey ₄ , Nicholas K Proctor ₄ , Xiyun Chai ₄ , Sergey Shcherbinin ₄ , John R Sims ₄ , Gallen Triana-Baltzer ₅ , Clara Theunis ₆ , Randy Slemmon ₅ , Marc Mercken ₆ , Hartmuth Kolb ₅ , Jeffrey L Dage ₄ , Oskar Hansson _{1,

7}

Affiliation

Cerebrospinal fluid (CSF) p-tau181 (tau phosphorylated at threonine 181) is an established biomarker of Alzheimer's disease (AD), reflecting abnormal tau metabolism in the brain. Here we investigate the performance of CSF p-tau217 as a biomarker of AD in comparison to p-tau181. In the Swedish BioFINDER cohort (n = 194), p-tau217 shows stronger correlations with the tau positron emission tomography (PET) tracer [18F]flortaucipir, and more accurately identifies individuals with abnormally increased [18F]flortaucipir retention. Furthermore, longitudinal increases in p-tau217 are higher compared to p-tau181 and better correlate with [18F]flortaucipir uptake. P-tau217 correlates better than p-tau181 with CSF and PET measures of neocortical amyloid-β burden and more accurately distinguishes AD dementia from non-AD neurodegenerative disorders. Higher correlations between p-tau217 and [18F]flortaucipir are corroborated in an independent EXPEDITION3 trial cohort (n = 32). The main results are validated using a different p-tau217 immunoassay. These findings suggest that p-tau217 might be more useful than p-tau181 in the diagnostic work up of AD.

中文翻译：

脑脊液 p-tau217 作为阿尔茨海默病的生物标志物表现优于 p-tau181。

脑脊液 (CSF) p-tau181（tau 在苏氨酸 181 处磷酸化）是阿尔茨海默病 (AD) 的既定生物标志物，反映了大脑中异常的 tau 代谢。在这里，我们与 p-tau181 相比，研究了 CSF p-tau217 作为 AD 生物标志物的性能。在瑞典 BioFINDER 队列 (n = 194) 中，p-tau217 显示与 tau 正电子发射断层扫描 (PET) 示踪剂 [18F]flortaucipir 更强的相关性，并且可以更准确地识别 [18F]flortaucipir 保留异常增加的个体。此外，与 p-tau181 相比，p-tau217 的纵向增加更高，并且与 [18F]flortaucipir 摄取相关性更好。 P-tau217 比 p-tau181 与 CSF 和 PET 测量新皮质β淀粉样蛋白负荷的相关性更好，并且可以更准确地区分 AD 痴呆和非 AD 神经退行性疾病。 p-tau217 和 [18F]flortaucipir 之间较高的相关性在独立的 EXPEDITION3 试验队列 (n = 32) 中得到证实。主要结果使用不同的 p-tau217 免疫测定进行验证。这些发现表明 p-tau217 在 AD 的诊断工作中可能比 p-tau181 更有用。

更新日期：2020-04-24

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