Performance of a fully-automated Lumipulse plasma phospho-tau181 assay for Alzheimer's disease.
Performance of a fully-automated Lumipulse plasma phospho-tau181 assay for Alzheimer's disease.
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用于阿尔茨海默病的全自动Lumipulse血浆磷酸化tau 181测定的性能。
DOI：
10.1186/s13195-022-01116-2
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发表时间：
2022-11-12
影响因子：
9
通讯作者：
Andreasson, Katrin I.
中科院分区：
文献类型：
--
作者：
Wilson, Edward N.;Young, Christina B.;Benitez, Javier Ramos;Swarovski, Michelle S.;Feinstein, Igor;Vandijck, Manu;Le Guen, Yann;Kasireddy, Nandita M.;Shahid, Marian;Corso, Nicole K.;Wang, Qian;Kennedy, Gabriel;Trelle, Alexandra N.;Lind, Betty;Channappa, Divya;Belnap, Malia;Ramirez, Veronica;Skylar-Scott, Irina;Younes, Kyan;Yutsis, Maya V.;Le Bastard, Nathalie;Quinn, Joseph F.;van Dyck, Christopher H.;Nairn, Angus;Fredericks, Carolyn A.;Tian, Lu;Kerchner, Geoffrey A.;Montine, Thomas J.;Sha, Sharon J.;Davidzon, Guido;Henderson, Victor W.;Longo, Frank M.;Greicius, Michael D.;Wagner, Anthony D.;Wyss-Coray, Tony;Poston, Kathleen L.;Mormino, Elizabeth C.;Andreasson, Katrin I.
最近阿尔茨海默病（AD）的疾病修饰疗法的前景加强了对早期疾病检测，诊断和治疗监测的准确生物标志物的需求。在开发用于AD的新型血液生物标志物方面的进展已经揭示了在各种残基处磷酸化的tau的血浆水平对AD痴呆是特异性的和敏感的。然而，目前可用的测试在访问、吞吐量和可扩展性方面存在缺陷，限制了广泛的实施。我们评估了用于检测AD的高通量全自动Lumipulse血浆p-tau 181检测的诊断和预后性能。从纵向斯坦福大学阿尔茨海默病研究中心（ADRC）和斯坦福大学衰老和记忆研究（SAMS）队列中获得来自老年临床未受损个体（CU，n = 463）和患有轻度认知障碍（MCI，n = 107）或AD痴呆（n = 78）的患者的血浆。我们评估了血浆p-tau 181对临床AD诊断的鉴别准确性、与淀粉样β肽和CSF中p-tau 181浓度的相关性、与淀粉样蛋白正电子发射断层扫描（PET）的相关性以及预测纵向认知和功能变化的能力。该试验在区分AD与对照受试者方面表现出稳健的性能（AUC 0.959，CI：0.912至0.990），并且与CSF p-tau 181、CSF Aβ42/Aβ40比值和淀粉样蛋白-PET总体SUVR密切相关。在Aβ+和Aβ−组中分别检查时，血浆p-tau 181与CSF生物标志物之间的相关性显著。血浆p-tau 181在CU和AD诊断组中随时间显著增加。在控制了临床诊断、年龄、性别和教育程度后，基线血浆p-tau 181预测了AD组在长达5年的随访期间莫卡总体变化和CDR盒总和的变化。因此，这种全自动和可用的基于血液的生物标志物测定可用于AD的早期检测、诊断、预后和治疗监测。在线版本包含补充材料，可通过10.1186/s13195-022-01116-2获得。
The recent promise of disease-modifying therapies for Alzheimer’s disease (AD) has reinforced the need for accurate biomarkers for early disease detection, diagnosis and treatment monitoring. Advances in the development of novel blood-based biomarkers for AD have revealed that plasma levels of tau phosphorylated at various residues are specific and sensitive to AD dementia. However, the currently available tests have shortcomings in access, throughput, and scalability that limit widespread implementation. We evaluated the diagnostic and prognostic performance of a high-throughput and fully-automated Lumipulse plasma p-tau181 assay for the detection of AD. Plasma from older clinically unimpaired individuals (CU, n = 463) and patients with mild cognitive impairment (MCI, n = 107) or AD dementia (n = 78) were obtained from the longitudinal Stanford University Alzheimer’s Disease Research Center (ADRC) and the Stanford Aging and Memory Study (SAMS) cohorts. We evaluated the discriminative accuracy of plasma p-tau181 for clinical AD diagnosis, association with amyloid β peptides and p-tau181 concentrations in CSF, association with amyloid positron emission tomography (PET), and ability to predict longitudinal cognitive and functional change. The assay showed robust performance in differentiating AD from control participants (AUC 0.959, CI: 0.912 to 0.990), and was strongly associated with CSF p-tau181, CSF Aβ42/Aβ40 ratio, and amyloid-PET global SUVRs. Associations between plasma p-tau181 with CSF biomarkers were significant when examined separately in Aβ+ and Aβ− groups. Plasma p-tau181 significantly increased over time in CU and AD diagnostic groups. After controlling for clinical diagnosis, age, sex, and education, baseline plasma p-tau181 predicted change in MoCA overall and change in CDR Sum of Boxes in the AD group over follow-up of up to 5 years. This fully-automated and available blood-based biomarker assay therefore may be useful for early detection, diagnosis, prognosis, and treatment monitoring of AD. The online version contains supplementary material available at 10.1186/s13195-022-01116-2.
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DOI：
10.1084/jem.20200861
发表时间：
2020-11-02
期刊：
The Journal of experimental medicine
影响因子：
--
作者：
Barthélemy NR;Horie K;Sato C;Bateman RJ
通讯作者：
Bateman RJ
影响因子：
12.7
作者：
Ashton NJ;Pascoal TA;Karikari TK;Benedet AL;Lantero-Rodriguez J;Brinkmalm G;Snellman A;Schöll M;Troakes C;Hye A;Gauthier S;Vanmechelen E;Zetterberg H;Rosa-Neto P;Blennow K
通讯作者：
Blennow K
DOI：
10.1007/s00259-020-05120-2
发表时间：
2021-07
影响因子：
9.1
作者：
Boccardi M;Dodich A;Albanese E;Gayet-Ageron A;Festari C;Ashton NJ;Bischof GN;Chiotis K;Leuzy A;Wolters EE;Walter MA;Rabinovici GD;Carrillo M;Drzezga A;Hansson O;Nordberg A;Ossenkoppele R;Villemagne VL;Winblad B;Frisoni GB;Garibotto V
通讯作者：
Garibotto V
DOI：
10.1007/s00259-021-05253-y
发表时间：
2021-07
影响因子：
9.1
作者：
Ashton NJ;Leuzy A;Karikari TK;Mattsson-Carlgren N;Dodich A;Boccardi M;Corre J;Drzezga A;Nordberg A;Ossenkoppele R;Zetterberg H;Blennow K;Frisoni GB;Garibotto V;Hansson O
通讯作者：
Hansson O
DOI：
10.1038/s41572-021-00269-y
发表时间：
2021-05-13
期刊：
Nature reviews. Disease primers
影响因子：
--
作者：
Knopman DS;Amieva H;Petersen RC;Chételat G;Holtzman DM;Hyman BT;Nixon RA;Jones DT
通讯作者：
Jones DT