CSF sAPPβ, YKL-40, and neurofilament light in frontotemporal lobar degeneration
CSF sAPPβ, YKL-40, and neurofilament light in frontotemporal lobar degeneration
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DOI：
10.1212/wnl.0000000000004088
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发表时间：
2017-07-11
期刊：
影响因子：
9.9
通讯作者：
Lleo, Alberto
中科院分区：
文献类型：
--
作者：
Alcolea, Daniel;Vilaplana, Eduard;Lleo, Alberto
目的：分析3种CSF生物标志物的临床效用及其在额颞叶变性（FTLD）谱内患有不同痴呆和帕金森综合征的大型患者队列中的结构成像相关性。我们分析了3种CSF生物标志物，（YKL-40，淀粉样前体蛋白的可溶性β片段[sAPP β]，神经丝轻[NfL]）和核心阿尔茨海默病（AD）生物标志物（β-淀粉样蛋白（1-42）、总tau蛋白、磷酸化tau蛋白）（n = 159）：额颞叶痴呆的行为变体（n = 68）、原发性进行性失语的非流利变体（n = 23）和语义变体（n = 19）、进行性核上性麻痹（n = 28）和皮质基底综合征（n = 21）。我们还包括AD患者（n = 72）和认知正常对照组（CN; n 5 - 76）。我们比较了组间的横截面生物标志物水平，研究了它们与皮质厚度的相关性，并评估了它们潜在的诊断utility.Results：FTLD相关综合征患者的sAPP β水平低于CN和AD患者。sAPP β水平与额叶和扣带回区的皮质结构变化有很强的相关性。与对照组相比，FTLD和AD组中的NfL和YKL-40水平均较高。在受试者操作特征分析中，sAPP β/YKL-40和NfL/sAPP β比值的曲线下面积分别为0.91和0.96，区分FTLD患者和CN患者，以及0.84和0.85，区分FTLD患者和AD患者。在临床实践中，sAPP β与YKL-40和CSF中的NfL的组合可用于增加FTLD相关综合征的诊断的确定性。证据分类：本研究提供了III类证据，证明CSF中sAPP β、YKL-40和NfL水平可用于识别FTLD相关综合征患者。
Objective: To analyze the clinical utility of 3 CSF biomarkers and their structural imaging correlates in a large cohort of patients with different dementia and parkinsonian syndromes within the spectrum of frontotemporal lobar degeneration (FTLD).Methods: We analyzed 3 CSF biomarkers (YKL-40, soluble beta fragment of amyloid precursor protein [sAPP beta], neurofilament light [NfL]) and core Alzheimer disease (AD) biomarkers (beta-amyloid(1-42), total tau, phosphorylated tau) in patients with FTLD-related clinical syndromes (n = 159): behavioral variant of frontotemporal dementia (n = 68), nonfluent (n = 23) and semantic (n = 19) variants of primary progressive aphasia, progressive supranuclear palsy (n = 28), and corticobasal syndrome (n = 21). We also included patients with AD (n = 72) and cognitively normal controls (CN; n 5 76). We compared cross-sectional biomarker levels between groups, studied their correlation with cortical thickness, and evaluated their potential diagnostic utility.Results: Patients with FTLD-related syndromes had lower levels of sAPP beta than CN and patients with AD. The levels of sAPP beta showed a strong correlation with cortical structural changes in frontal and cingulate areas. NfL and YKL-40 levels were high in both the FTLD and AD groups compared to controls. In the receiver operating characteristic analysis, the sAPP beta/YKL-40 and NfL/sAPP beta ratios had areas under the curve of 0.91 and 0.96, respectively, distinguishing patients with FTLD from CN, and of 0.84 and 0.85, distinguishing patients with FTLD from patients with AD.Conclusions: The combination of sAPP beta with YKL-40 and with NfL in CSF could be useful to increase the certainty of the diagnosis of FTLD-related syndromes in clinical practice. Classification of evidence: This study provides Class III evidence that CSF levels of sAPP beta, YKL-40, and NfL are useful to identify patients with FTLD-related syndromes.