A two-step workflow based on plasma p-tau217 to screen for amyloid β positivity with further confirmatory testing only in uncertain cases.
A two-step workflow based on plasma p-tau217 to screen for amyloid β positivity with further confirmatory testing only in uncertain cases.
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DOI：
10.1038/s43587-023-00471-5
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发表时间：
2023-09
期刊：
影响因子：
--
通讯作者：
Hansson, Oskar
中科院分区：
文献类型：
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作者：
Brum, Wagner S.;Cullen, Nicholas C.;Janelidze, Shorena;Ashton, Nicholas J.;Zimmer, Eduardo R.;Therriault, Joseph;Benedet, Andrea L.;Rahmouni, Nesrine;Tissot, Cecile;Stevenson, Jenna;Servaes, Stijn;Triana-Baltzer, Gallen;Kolb, Hartmuth C.;Palmqvist, Sebastian;Stomrud, Erik;Rosa-Neto, Pedro;Blennow, Kaj;Hansson, Oskar
随着抗A β免疫疗法最近被批准用于阿尔茨海默病（AD），迫切需要用于识别认知障碍患者中淀粉样蛋白（Aβ）阳性的具有成本效益的策略。血液生物标志物可以准确地检测AD病理，但目前尚不清楚将其纳入完整的诊断工作流程是否可以减少在准确分类患者时所需的确认性脑脊液（CSF）或正电子发射断层扫描（PET）测试的数量。我们评估了两个步骤的工作流程，用于确定来自两个独立的基于记忆诊所的队列（n = 348）的轻度认知障碍（MCI）患者的Aβ-PET状态。在BioFINDER-1中开发了包括血浆tau蛋白217（p-tau 217）、年龄和APOE ε4状态的血液模型（曲线下面积（AUC）= 89.3%），并在BioFINDER-2中进行了验证（AUC = 94.3%）。在步骤1中，使用基于血液的模型将患者分层为Aβ-PET阳性的低、中或高风险。在第2步中，我们假设仅将中度风险患者转诊至CSF Aβ42/Aβ40检测，而仅第1步确定低风险和高风险组的Aβ状态。根据第1步中使用的是宽松、中等还是严格阈值，两步工作流程检测Aβ-PET状态的总体准确度分别为88.2%、90.5%和92.0%，同时将必要的CSF检测次数分别减少85.9%、72.7%和61.2%。在次要分析中，BioFINDER-1模型的改编版本成功验证了TRIAD队列（n = 84）认知障碍患者中采用不同血浆p-tau 217免疫测定的两步工作流程。总之，使用基于血浆p-tau 217的模型对MCI患者进行风险分层，可以在准确分类患者的同时大大减少对确证性检测的需求，为在记忆诊所环境中检测AD提供了一种具有成本效益的策略。基于血浆p-tau 217的风险分层可以大大减少在认知障碍患者中筛查Aβ阳性时对侵入性或昂贵检测的需求，为支持阿尔茨海默病诊断提供了一种具有成本效益的策略。
Cost-effective strategies for identifying amyloid-β (Aβ) positivity in patients with cognitive impairment are urgently needed with recent approvals of anti-Aβ immunotherapies for Alzheimer’s disease (AD). Blood biomarkers can accurately detect AD pathology, but it is unclear whether their incorporation into a full diagnostic workflow can reduce the number of confirmatory cerebrospinal fluid (CSF) or positron emission tomography (PET) tests needed while accurately classifying patients. We evaluated a two-step workflow for determining Aβ-PET status in patients with mild cognitive impairment (MCI) from two independent memory clinic-based cohorts (n = 348). A blood-based model including plasma tau protein 217 (p-tau217), age and APOE ε4 status was developed in BioFINDER-1 (area under the curve (AUC) = 89.3%) and validated in BioFINDER-2 (AUC = 94.3%). In step 1, the blood-based model was used to stratify the patients into low, intermediate or high risk of Aβ-PET positivity. In step 2, we assumed referral only of intermediate-risk patients to CSF Aβ42/Aβ40 testing, whereas step 1 alone determined Aβ-status for low- and high-risk groups. Depending on whether lenient, moderate or stringent thresholds were used in step 1, the two-step workflow overall accuracy for detecting Aβ-PET status was 88.2%, 90.5% and 92.0%, respectively, while reducing the number of necessary CSF tests by 85.9%, 72.7% and 61.2%, respectively. In secondary analyses, an adapted version of the BioFINDER-1 model led to successful validation of the two-step workflow with a different plasma p-tau217 immunoassay in patients with cognitive impairment from the TRIAD cohort (n = 84). In conclusion, using a plasma p-tau217-based model for risk stratification of patients with MCI can substantially reduce the need for confirmatory testing while accurately classifying patients, offering a cost-effective strategy to detect AD in memory clinic settings. Risk stratification based on plasma p-tau217 can substantially reduce the need for invasive or expensive testing when screening for Aβ positivity in patients with cognitive impairment, offering a cost-effective strategy to support an Alzheimer’s disease diagnosis.
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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
影响因子：
29
作者：
Erickson, Pontus;Simren, Joel;Brum, Wagner S.;Ennis, Gilda E.;Kollmorgen, Gwendlyn;Suridjan, Ivonne;Langhough, Rebecca;Jonaitis, Erin M.;Van Hulle, Carol A.;Betthauser, Tobey J.;Carlsson, Cynthia M.;Asthana, Sanjay;Ashton, Nicholas J.;Johnson, Sterling C.;Shaw, Leslie M.;Blennow, Kaj;Andreasson, Ulf;Bendlin, Barbara B.;Zetterberg, Henrik
通讯作者：
Zetterberg, Henrik
DOI：
10.3233/jad-170203
发表时间：
2017
期刊：
Journal of Alzheimer's disease : JAD
影响因子：
--
作者：
Borland E;Nägga K;Nilsson PM;Minthon L;Nilsson ED;Palmqvist S
通讯作者：
Palmqvist S
影响因子：
14
作者：
Binette, Alexa Pichet;Janelidze, Shorena;Cullen, Nicholas;Dage, Jeffrey L.;Bateman, Randall J.;Zetterberg, Henrik;Blennow, Kaj;Stomrud, Erik;Mattsson-Carlgren, Niklas;Hansson, Oskar
通讯作者：
Hansson, Oskar
DOI：
10.1186/s13195-022-01005-8
发表时间：
2022-05-14
期刊：
Alzheimer's research & therapy
影响因子：
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作者：
通讯作者：
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