The relationship between cerebrospinal fluid markers of Alzheimer pathology and positron emission tomography tau imaging
The relationship between cerebrospinal fluid markers of Alzheimer pathology and positron emission tomography tau imaging
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DOI：
10.1093/brain/aww139
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发表时间：
2016-08-01
期刊：
影响因子：
14.5
通讯作者：
Benzinger, Tammie L. S.
中科院分区：
文献类型：
--
作者：
Gordon, Brian A.;Friedrichsen, Karl;Benzinger, Tammie L. S.
阿尔茨海默病的两种主要分子病理是淀粉样斑块和tau免疫反应性神经原纤维缠结。对这些病理的调查仅限于脑脊液分析和可以成像淀粉样斑块的正电子发射断层扫描示踪剂。Tau示踪剂最近被引入该领域，尽管示踪剂的效用及其与其他阿尔茨海默病生物标志物的关系尚不清楚。在这里，我们使用放射性tau配体F-18-AV-1451（以前称为T807）检查了41名认知正常和11名认知受损的老年人的tau沉积，这些老年人也接受了腰椎穿刺以评估脑脊液中总tau（t-tau）、磷酸化tau(181) （p-tau(181)）和淀粉样蛋白- β(42)的水平。体素统计分析检查了与认知障碍相关的tau沉积的空间模式。然后，我们将tau示踪剂的摄取量与脑脊液生物标志物的水平联系起来。所有的分析都控制了年龄和性别，如果合适的话，还控制了成像和腰椎穿刺评估之间的时间。有症状的个体（临床痴呆评分b>）显示tau示踪剂摄取水平明显增加。这种升高在颞叶和颞顶叶交界处最为明显，但更广泛地扩展到顶叶和额叶皮层。在整个队列中，所有脑脊液生物标志物与示踪剂摄取之间存在显著关系，特别是tau相关的脑脊液标志物。在控制β淀粉样蛋白水平（42）后，与tau摄取的相关性为，t-tau为r = 0.490 (P < 0.001)， P -tau为r = 0.492 (P < 0.001)（181）。在认知正常的队列中，淀粉样蛋白- β水平（42,）而不是t-tau或p-tau水平（181）与主要局限于内侧颞叶和邻近新皮层区域的示踪剂结合升高相关。AV-1451 tau蛋白在内侧颞叶、顶叶和额叶皮层的结合与tau蛋白相关的脑脊液测量相关。在临床前阿尔茨海默病中，内侧颞叶和邻近皮层有局灶性脑损伤。
The two primary molecular pathologies in Alzheimer's disease are amyloid-beta plaques and tau-immunoreactive neurofibrillary tangles. Investigations into these pathologies have been restricted to cerebrospinal fluid assays, and positron emission tomography tracers that can image amyloid-beta plaques. Tau tracers have recently been introduced into the field, although the utility of the tracer and its relationship to other Alzheimer biomarkers are still unknown. Here we examined tau deposition in 41 cognitively normal and 11 cognitively impaired older adults using the radioactive tau ligand F-18-AV-1451 (previously known as T807) who also underwent a lumbar puncture to assess cerebrospinal fluid levels of total tau (t-tau), phosphorylated tau(181) (p-tau(181)) and amyloid-beta(42). Voxel-wise statistical analyses examined spatial patterns of tau deposition associated with cognitive impairment. We then related the amount of tau tracer uptake to levels of cerebrospinal fluid biomarkers. All analyses controlled for age and gender and, when appropriate, the time between imaging and lumbar puncture assessments. Symptomatic individuals (Clinical Dementia Rating > 0) demonstrated markedly increased levels of tau tracer uptake. This elevation was most prominent in the temporal lobe and temporoparietal junction, but extended more broadly into parietal and frontal cortices. In the entire cohort, there were significant relationships among all cerebrospinal fluid biomarkers and tracer uptake, notably for tau-related cerebrospinal fluid markers. After controlling for levels of amyloid-beta(42,) the correlations with tau uptake were r = 0.490 (P < 0.001) for t-tau and r = 0.492 (P < 0.001) for p-tau(181). Within the cognitively normal cohort, levels of amyloid-beta(42,) but not t-tau or p-tau(181), were associated with elevated tracer binding that was confined primarily to the medial temporal lobe and adjacent neocortical regions. AV-1451 tau binding in the medial temporal, parietal, and frontal cortices is correlated with tau-related cerebrospinal fluid measures. In preclinical Alzheimer's disease, there is focal tauopathy in the medial temporal lobes and adjacent cortices.