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

被引：318

作者：

Janelidze, Shorena ^{[1
]}

Stomrud, Erik ^{[1
]}

Smith, Ruben ^{[1
,2
]}

Palmqvist, Sebastian ^{[1
,2
]}

Mattsson, Niklas ^{[1
,2
,3
]}

Airey, David C. ^{[4
]}

Proctor, Nicholas K. ^{[4
]}

Chai, Xiyun ^{[4
]}

Shcherbinin, Sergey ^{[4
]}

Sims, John R. ^{[4
]}

Triana-Baltzer, Gallen ^{[5
]}

Theunis, Clara ^{[6
]}

Slemmon, Randy ^{[5
]}

Mercken, Marc ^{[6
]}

Kolb, Hartmuth ^{[5
]}

Dage, Jeffrey L. ^{[4
]}

Hansson, Oskar ^{[1
,7
]}

机构：

[1] Lund Univ, Clin Memory Res Unit, Solvegatan 18, Lund, Sweden

[2] Skane Univ Hosp, Dept Neurol, Entregatan 7, S-22242 Lund, Sweden

[3] Lund Univ, Wallenberg Ctr Mol Med, Klin Gatan 32, S-22184 Lund, Sweden

[4] Eli Lilly & Co, Indianapolis, IN 46285 USA

[5] Janssen Res & Dev, Neurosci Biomarkers, 3210 Merryfield Row, San Diego, CA 92121 USA

[6] Johnson & Johnson, Janssen Pharmaceut Co, Turnhoutseweg 30, B-2340 Beerse, Belgium

[7] Skane Univ Hosp, Memory Clin, Simrisbanvagen 14, S-20502 Malmo, Sweden

来源：

NATURE COMMUNICATIONS | 2020年 / 11卷 / 01期

基金：

欧洲研究理事会; 瑞典研究理事会;

关键词：

POSITRON-EMISSION-TOMOGRAPHY; MILD COGNITIVE IMPAIRMENT; BETA-AMYLOID; 42; CSF T-TAU; DIAGNOSTIC-CRITERIA; NEUROFIBRILLARY PATHOLOGY; SEQUENTIAL PHOSPHORYLATION; ASSOCIATION WORKGROUPS; NATIONAL INSTITUTE; CROSS-VALIDATION;

D O I：

10.1038/s41467-020-15436-0

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

07 ; 0710 ; 09 ;

摘要：

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 [F-18]flortaucipir, and more accurately identifies individuals with abnormally increased [F-18]flortaucipir retention. Furthermore, longitudinal increases in p-tau217 are higher compared to p-tau181 and better correlate with [F-18]flortaucipir uptake. P-tau217 correlates better than p-tau181 with CSF and PET measures of neocortical amyloid-beta burden and more accurately distinguishes AD dementia from non-AD neurodegenerative disorders. Higher correlations between p-tau217 and [F-18]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. 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 AD brain. Here the authors demonstrate that CSF p-tau217 shows better performance as an AD biomarker than p-tau181.

引用

页数：12

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