Shcherbinin Sergey, Morris Amanda, Higgins Ixavier A, Tunali Ilke, Lu Ming, Deveau Carmen, Southekal Sudeepti, Kotari Vikas, Evans Cynthia D, Arora Anupa K, Collins Emily C, Pontecorvo Michael, Mintun Mark A, Sims John R
Eli Lilly and Company Indianapolis Indiana USA.
Avid Radiopharmaceuticals Philadelphia Pennsylvania USA.
Alzheimers Dement (N Y). 2023 Aug 16;9(3):e12415. doi: 10.1002/trc2.12415. eCollection 2023 Jul-Sep.
Alzheimer's disease (AD) is characterized by the presence of both amyloid and tau pathology. In vivo diagnosis can be made with amyloid and tau positron emission tomography (PET) imaging. Emergent evidence supports that amyloid and tau accumulation are associated and that amyloid accumulation may precede that of tau. This report further investigates the relationship between amyloid and tau to assess whether elevated cortical tau can predict elevated amyloid in participants with early symptomatic AD.
Florbetapir F18 and flortaucipir F18 uptake were evaluated from baseline PET scans collected in three multi-center studies with cognitively impaired participants, including A05 ( = 306; NCT02016560), TB ( = 310; TRAILBLAZER-ALZ; NCT03367403), and TB2 ( = 1165; TRAILBLAZER-ALZ 2; NCT04437511). Images were assessed using visual and quantitative approaches to establish amyloid (A+) and tau (T+) positivity, as well as a combination method (tauVQ) to establish T+. Associations between global amyloid and tau were evaluated with positive and negative predictive values (PPV, NPV) and likelihood ratios (LR+, LR-). Predictive values within subgroups according to ethnicity, race, cognitive score, age, and sex were also evaluated. The relationship between regional tau (four target and two reference regions were tested) and global amyloid was investigated in A05 participant scans using receiver-operating characteristic (ROC) curves.
PPV for amyloid positivity was ≥93% for all three trials using various A+ and T+ definitions, including visual, quantitative, and combination methods. Population characteristics did not have an impact on A+ predictability. Regional analyses (early tau (Eτ) volume of interest (VOI), temporal, parietal, frontal) revealed significant area under the ROC curve in Eτ VOI compared to frontal region, regardless of reference region and consistent among visual and quantitative A+ definitions ( < 0.001).
These findings suggest that a positive tau PET scan is associated (≥93%) with amyloid positivity in individuals with early symptomatic AD, with the potential benefits of reducing clinical trial and health care expenses, radiation exposure, and participant time.
Positron emission tomography (PET) evaluates candidates for Alzheimer's disease (AD) research. A positive tau PET scan is associated (≥93%) with amyloid positivity.A positive amyloid PET is not necessarily associated with tau positivity.Tau PET could be the sole diagnostic tool to confirm candidates for AD trials.
阿尔茨海默病（AD）的特征是存在淀粉样蛋白和tau蛋白病变。可通过淀粉样蛋白和tau蛋白正电子发射断层扫描（PET）成像进行体内诊断。新出现的证据支持淀粉样蛋白和tau蛋白的积累是相关的，并且淀粉样蛋白的积累可能先于tau蛋白。本报告进一步研究淀粉样蛋白和tau蛋白之间的关系，以评估在早期有症状的AD参与者中，皮质tau蛋白升高是否能预测淀粉样蛋白升高。
在三项针对认知受损参与者的多中心研究中收集的基线PET扫描中，评估了氟代硼替吡F18和氟代托卡匹F18的摄取情况，这些研究包括A05（n = 306；NCT02016560）、TB（n = 310；TRAILBLAZER - ALZ；NCT03367403）和TB2（n = 1165；TRAILBLAZER - ALZ 2；NCT04437511）。使用视觉和定量方法评估图像，以确定淀粉样蛋白（A +）和tau蛋白（T +）阳性，以及使用一种组合方法（tauVQ）来确定T +。使用阳性和阴性预测值（PPV、NPV）和似然比（LR +、LR -）评估整体淀粉样蛋白和tau蛋白之间的关联。还评估了根据种族、民族、认知评分、年龄和性别的亚组内的预测值。在A05参与者的扫描中，使用受试者工作特征（ROC）曲线研究区域tau蛋白（测试了四个目标区域和两个参考区域）与整体淀粉样蛋白之间的关系。
使用包括视觉、定量和组合方法在内的各种A +和T +定义，所有三项试验中淀粉样蛋白阳性的PPV均≥93%。人群特征对A +的可预测性没有影响。区域分析（早期tau蛋白（Eτ）感兴趣体积（VOI）、颞叶、顶叶、额叶）显示，与额叶区域相比，Eτ VOI的ROC曲线下面积显著，无论参考区域如何，并且在视觉和定量A +定义中是一致的（P < 0.001）。
这些发现表明，在早期有症状的AD个体中，tau蛋白PET扫描阳性与淀粉样蛋白阳性相关（≥93%），具有减少临床试验和医疗费用、辐射暴露以及参与者时间的潜在益处。
正电子发射断层扫描（PET）评估阿尔茨海默病（AD）研究的候选者。tau蛋白PET扫描阳性与淀粉样蛋白阳性相关（≥93%）。淀粉样蛋白PET阳性不一定与tau蛋白阳性相关。tau蛋白PET可能是确认AD试验候选者的唯一诊断工具。
