Neuronal pentraxin receptor-1 is a new cerebrospinal fluid biomarker of Alzheimer's disease progression.
Neuronal pentraxin receptor-1 is a new cerebrospinal fluid biomarker of Alzheimer's disease progression.
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DOI：
10.12688/f1000research.15095.1
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发表时间：
2018
期刊：
影响因子：
--
通讯作者：
Diamandis EP
中科院分区：
文献类型：
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作者：
Begcevic I;Tsolaki M;Brinc D;Brown M;Martinez-Morillo E;Lazarou I;Kozori M;Tagaraki F;Nenopoulou S;Gkioka M;Lazarou E;Lim B;Batruch I;Diamandis EP
背景：阿尔茨海默病（AD）是最常见的痴呆类型，临床症状逐渐出现。主要病理特征是细胞外β淀粉样斑块和细胞内神经原纤维缠结（NFT）的脑沉积。脑脊液反映大脑的病理变化；淀粉样蛋白 β 1-42 是淀粉样斑块的标志物，而总 tau 蛋白和磷酸化 tau 蛋白是 NFT 形成的标志物。为了更好的预后、更具体的诊断、预测疾病的严重程度和进展以及改善临床试验中的患者分类，需要与疾病发病机制相关的其他生物标志物。本研究的目的是评估大脑特异性蛋白质作为 AD 进展的潜在生物标志物。 方法：总体而言，使用基于质谱的选择性反应监测测定法对轻度认知障碍 (MCI) 和轻度、中度和重度 AD 痴呆 (n=101) 患者的脑脊液 (CSF) 样本中的 30 种候选蛋白进行了定量。 ELISA 用于神经元五聚蛋白受体 1 (NPTXR) 确认。 结果：观察到蛋白 NPTXR（曲线下面积，AUC=0.799）可以最好地区分 MCI 和更晚期的 AD 阶段（中度和重度痴呆）。在两组之间观察到这种蛋白质的丰度存在统计学差异，严重 AD 患者的水平逐渐降低 (p<0.05)。 ELISA 证实，在包括对照组、MCI 和 AD 患者在内的单独队列中，AD 的水平较低。 结论：我们得出结论，脑脊液中的 NPTXR 蛋白是 AD 进展的一种新型潜在生物标志物，在评估临床试验中治疗成功方面可能具有重要用途。
Background: Alzheimer’s disease (AD) is the most common type of dementia, with progressive onset of clinical symptoms. The main pathological hallmarks are brain deposits of extracellular amyloid beta plaques and intracellular neurofibrillary tangles (NFT). Cerebrospinal fluid reflects pathological changes in the brain; amyloid beta 1-42 is a marker of amyloid plaques, while total and phosphorylated tau are markers of NFT formation. Additional biomarkers associated with disease pathogenesis are needed, for better prognosis, more specific diagnosis, prediction of disease severity and progression and for improved patient classification in clinical trials. The aim of the present study was to evaluate brain-specific proteins as potential biomarkers of progression of AD. Methods: Overall, 30 candidate proteins were quantified in cerebrospinal fluid (CSF) samples from patients with mild cognitive impairment (MCI) and mild, moderate and severe AD dementia (n=101) using mass spectrometry-based selected reaction monitoring assays. ELISA was used for neuronal pentraxin receptor-1 (NPTXR) confirmation. Results: The best discrimination between MCI and more advanced AD stages (moderate and severe dementia) was observed for protein NPTXR (area under the curve, AUC=0.799). A statistically different abundance of this protein was observed between the two groups, with severe AD patients having progressively lower levels (p<0.05). ELISA confirmed lower levels in AD, in a separate cohort that included controls, MCI and AD patients. Conclusions: We conclude that NPTXR protein in CSF is a novel potential biomarker of AD progression and could have important utility in assessing treatment success in clinical trials.