The validation status of blood biomarkers of amyloid and phospho-tau assessed with the 5-phase development framework for AD biomarkers.
The validation status of blood biomarkers of amyloid and phospho-tau assessed with the 5-phase development framework for AD biomarkers.
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DOI：
10.1007/s00259-021-05253-y
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发表时间：
2021-07
影响因子：
9.1
通讯作者：
Hansson O
中科院分区：
文献类型：
--
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
反映阿尔茨海默病（AD）病理生理学的血液生物标志物（磷酸化tau蛋白和淀粉样蛋白-β）的发展为痴呆鉴别诊断和早期检测提供了可扩展的测试潜力。2019年，日内瓦AD生物标志物路线图倡议将血液生物标志物纳入AD生物标志物的系统验证。专家小组于2019年11月在日内瓦举行了为期两天的研讨会。基于生物标志物路线图方法评估了血液生物标志物的成熟度水平（完全达到、部分达到、初步证据、未达到、不成功），并在研讨会期间进行了充分讨论，研讨会还评估了脑脊液（CSF）和正电子发射断层扫描（PET）生物标志物。血浆p-tau已显示出分析有效性（II期主要目的1）和临床有效性的第一个证据（III期主要目的1），而Aβ的成熟度水平仍有待部分实现。已分别指定p-tau和Aβ完全和部分实现，因为它们与死前测量相关（第2阶段次要目标2）。然而，仅存在协变量、试验比较和临界值标准影响的初步证据。尽管血液生物标志物相对婴儿期，但与CSF生物标志物相比，1期至3期已经取得了很大进展-其中p-tau在检测AD和预测疾病进展方面取得了更大的成功。然而，缺乏关于协变量对生物标志物测量的影响的足够数据。第4阶段（实际业绩）或第5阶段（影响/成本评估）的目标均未经过测试，因此未实现。
The development of blood biomarkers that reflect Alzheimer’s disease (AD) pathophysiology (phosphorylated tau and amyloid-β) has offered potential as scalable tests for dementia differential diagnosis and early detection. In 2019, the Geneva AD Biomarker Roadmap Initiative included blood biomarkers in the systematic validation of AD biomarkers. A panel of experts convened in November 2019 at a two-day workshop in Geneva. The level of maturity (fully achieved, partly achieved, preliminary evidence, not achieved, unsuccessful) of blood biomarkers was assessed based on the Biomarker Roadmap methodology and discussed fully during the workshop which also evaluated cerebrospinal fluid (CSF) and positron emission tomography (PET) biomarkers. Plasma p-tau has shown analytical validity (phase 2 primary aim 1) and first evidence of clinical validity (phase 3 primary aim 1), whereas the maturity level for Aβ remains to be partially achieved. Full and partial achievement has been assigned to p-tau and Aβ, respectively, in their associations to ante-mortem measures (phase 2 secondary aim 2). However, only preliminary evidence exists for the influence of covariates, assay comparison and cut-off criteria. Despite the relative infancy of blood biomarkers, in comparison to CSF biomarkers, much has already been achieved for phases 1 through 3 – with p-tau having greater success in detecting AD and predicting disease progression. However, sufficient data about the effect of covariates on the biomarker measurement is lacking. No phase 4 (real-world performance) or phase 5 (assessment of impact/cost) aim has been tested, thus not achieved.
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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
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：
10.1084/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
了解细胞外TAU的复杂性有助于对阿尔茨海默氏病血液筛查的发展。
DOI：
10.1016/j.jalz.2018.09.010
发表时间：
2019-03
期刊：
Alzheimer's & dementia : the journal of the Alzheimer's Association
影响因子：
--
作者：
Chen Z;Mengel D;Keshavan A;Rissman RA;Billinton A;Perkinton M;Percival-Alwyn J;Schultz A;Properzi M;Johnson K;Selkoe DJ;Sperling RA;Patel P;Zetterberg H;Galasko D;Schott JM;Walsh DM
通讯作者：
Walsh DM
影响因子：
4.2
作者：
Chiotis, Konstantinos;Saint-Aubert, Laure;Nordberg, Agneta
通讯作者：
Nordberg, Agneta