Evaluation of Tau Imaging in Staging Alzheimer Disease and Revealing Interactions Between β-Amyloid and Tauopathy.
Evaluation of Tau Imaging in Staging Alzheimer Disease and Revealing Interactions Between β-Amyloid and Tauopathy.
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DOI：
10.1001/jamaneurol.2016.2078
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发表时间：
2016-09-01
期刊：
影响因子：
29
通讯作者：
Ances BM
中科院分区：
文献类型：
--
作者：
Wang L;Benzinger TL;Su Y;Christensen J;Friedrichsen K;Aldea P;McConathy J;Cairns NJ;Fagan AM;Morris JC;Ances BM
体内tau成像可能成为阿尔茨海默病（AD）的诊断标志物，并为阿尔茨海默病的病理生理学提供见解。评估[18F]-AV-1451正电子发射断层扫描（PET）成像对AD分期的有用性，并评估β-淀粉样蛋白（Aβ）、tau蛋白和体积损失之间的关系。密苏里州圣路易斯华盛顿大学的奈特阿尔茨海默病研究中心进行了一项成像研究。共纳入59名认知正常（CN）（临床痴呆评分[CDR]评分，0分）或AD痴呆（CDR评分，b>）的参与者。海马中[18F]-AV-1451的标准化摄取值比（SUVR）和优先定义的AD皮质特征区域、脑脊液a β42、海马体积和AD特征皮质厚度。在59名参与者中，38名（64%）是男性；平均（SD）年龄为74(6)岁。海马和AD皮质特征区的[18F]-AV-1451 SUVR将AD与CN参与者区分开来（受试者工作特征曲线下面积范围[95% CI]， 0.89[0.73-1.00]至0.98[0.92-1.00]）。AD皮质特征区[18F]-AV-1451 SUVR截断值为1.19（敏感性100%，特异性86−），可将脑脊液Aβ42阳性（Aβ+） AD与脑脊液Aβ42阴性（Aβ−）CN受试者分开。同样的切断也将Aβ+ CN参与者分为低tau组和高tau组。此外，Aβ+的存在与AD皮质特征区[18F]-AV-1451 SUVR升高相关（Aβ+参与者：平均[SD]， 1.3 [0.3]； Aβ -参与者：1.1 [0.1];F = 4.3, P = 0.04），但在海马中没有。单独存在Aβ+与海马体积或AD特征皮质厚度无关。[18F]-AV-1451 SUVR升高与海马和AD皮质特征区体积损失有关。所观察到的[18F]-AV-1451的SUVR体积关联被海马中的Aβ状态所改变，但在AD皮层特征区没有。在Aβ+参与者中，海马[18F]-AV-1451 SUVR与体积呈负相关（R2 = 0.55; P < .001），而在Aβ -参与者中没有（R2 = 0; P = .97）。使用[18F]-AV-1451有可能对阿尔茨海默病的临床前和临床分期进行分期。β-淀粉样蛋白与海马和皮质损伤相互作用，影响神经变性。在缺乏Aβ的情况下，海马tau沉积可能不足以导致阿尔茨海默病的神经退行性过程。
In vivo tau imaging may become a diagnostic marker for Alzheimer disease (AD) and provides insights into the pathophysiology of AD. To evaluate the usefulness of [18F]-AV-1451 positron emission tomography (PET) imaging to stage AD and assess the associations among β-amyloid (Aβ), tau, and volume loss. An imaging study conducted at Knight Alzheimer Disease Research Center at Washington University in St Louis, Missouri. A total of 59 participants who were cognitively normal (CN) (Clinical Dementia Rating [CDR] score, 0) or had AD dementia (CDR score, >0) were included. Standardized uptake value ratio (SUVR) of [18F]-AV-1451 in the hippocampus and a priori-defined AD cortical signature regions, cerebrospinal fluid Aβ42, hippocampal volume, and AD signature cortical thickness. Of the 59 participants, 38 (64%) were male; mean (SD) age was 74 (6) years. The [18F]-AV-1451 SUVR in the hippocampus and AD cortical signature regions distinguished AD from CN participants (area under the receiver operating characteristic curve range [95% CI], 0.89 [0.73-1.00] to 0.98 [0.92-1.00]). An [18F]-AV-1451 SUVR cutoff value of 1.19 (sensitivity, 100%; specificity, 86−) from AD cortical signature regions best separated cerebrospinal fluid Aβ42-positive (Aβ+) AD from cerebrospinal fluid Aβ42-negative (Aβ−) CN participants. This same cutoff also divided Aβ+ CN participants into low vs high tau groups. Moreover, the presence of Aβ+ was associated with an elevated [18F]-AV-1451 SUVR in AD cortical signature regions (Aβ+ participants: mean [SD], 1.3 [0.3]; Aβ− participants: 1.1 [0.1]; F = 4.3, P = .04) but not in the hippocampus. The presence of Aβ+ alone was not related to hippocampal volume or AD signature cortical thickness. An elevated [18F]-AV-1451 SUVR was associated with volumetric loss in both the hippocampus and AD cortical signature regions. The observed [18F]-AV-1451 SUVR volumetric association was modified by Aβ status in the hippocampus but not in AD cortical signature regions. An inverse association between hippocampal [18F]-AV-1451 SUVR and volume was seen in Aβ+ participants (R2 = 0.55; P < .001) but not Aβ− (R2 = 0; P = .97) participants. Use of [18F]-AV-1451 has a potential for staging of the preclinical and clinical phases of AD. β-Amyloid interacts with hippocampal and cortical tauopathy to affect neurodegeneration. In the absence of Aβ, hippocampal tau deposition may be insufficient for the neurodegenerative process that leads to AD.