Association of Plasma Neurofilament Light With Neurodegeneration in Patients With Alzheimer Disease.
Association of Plasma Neurofilament Light With Neurodegeneration in Patients With Alzheimer Disease.
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DOI：
10.1001/jamaneurol.2016.6117
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发表时间：
2017-05-01
期刊：
影响因子：
29
通讯作者：
Alzheimer’s Disease Neuroimaging Initiative
中科院分区：
文献类型：
--
作者：
Mattsson N;Andreasson U;Zetterberg H;Blennow K;Alzheimer’s Disease Neuroimaging Initiative
血浆神经丝光在阿尔茨海默病中的重要性是什么？在这项对193名认知健康对照、197名轻度认知障碍患者和180名阿尔茨海默病痴呆患者的病例对照研究中，血浆神经丝光与阿尔茨海默病相关，并与认知能力下降、脑萎缩和脑代谢减退的未来进展相关。血浆神经丝光可能是阿尔茨海默病的一个有前途的非侵入性生物标志物。现有的用于阿尔茨海默病（AD）的脑脊液（CSF）或成像（tau正电子发射断层扫描）生物标志物是侵入性的或昂贵的。基于标准血液测试结果的生物标志物将在研究、药物开发和临床实践中有用。血浆神经丝光（NFL）最近被提出作为痴呆症神经变性的血液生物标志物。测试血浆NFL浓度是否在AD中增加，并与认知能力下降、其他AD生物标志物和神经退行性变的影像学证据相关。在这项前瞻性病例对照研究中，使用超灵敏测定法测量193名认知健康对照、197名轻度认知障碍（MCI）患者和180名阿尔茨海默病神经影像学倡议的AD痴呆患者的血浆NFL浓度。研究日期为2005年9月7日至2012年2月13日。血浆NFL分析于2016年9月进行。检测血浆NFL与诊断、Aβ病理特征、神经元损伤的CSF生物标志物、认知、脑结构和代谢之间的关联。在193名认知健康对照者、197名轻度认知障碍患者和180名AD伴痴呆患者中，血浆NFL与CSF NFL相关（斯皮尔曼ρ = 0.59，P <0.001）。与对照组（平均值34.7 ng/L）相比，MCI患者（平均值42.8 ng/L）和AD痴呆患者（平均值51.0 ng/L）的血浆NFL增加（P <0.001），并且AD痴呆患者与对照组相比具有较高的诊断准确性（受试者工作特征曲线下面积0.87，与已建立的CSF生物标志物相当）。血浆NFL在MCI患者和具有Aβ病理特征的AD痴呆患者中特别高。高血浆NFL与认知能力差和AD相关萎缩（基线和纵向）以及脑代谢低下（纵向）相关。血浆NFL与AD诊断以及该疾病的认知、生物化学和成像标志相关。这一发现意味着血浆NFL作为AD的非侵入性生物标志物的潜在有用性。这项病例对照研究比较了轻度认知功能障碍患者、AD痴呆患者和认知健康患者，以检测AD患者血浆神经丝光浓度是否增加，并与认知功能减退、其他AD生物标志物和神经退行性变的影像学证据相关。
What is the importance of plasma neurofilament light in Alzheimer disease? In this case-control study of 193 cognitively healthy controls, 197 patients with mild cognitive impairment, and 180 patients with Alzheimer disease dementia, plasma neurofilament light was associated with Alzheimer disease and correlated with future progression of cognitive decline, brain atrophy, and brain hypometabolism. Plasma neurofilament light may be a promising noninvasive biomarker for Alzheimer disease. Existing cerebrospinal fluid (CSF) or imaging (tau positron emission tomography) biomarkers for Alzheimer disease (AD) are invasive or expensive. Biomarkers based on standard blood test results would be useful in research, drug development, and clinical practice. Plasma neurofilament light (NFL) has recently been proposed as a blood-based biomarker for neurodegeneration in dementias. To test whether plasma NFL concentrations are increased in AD and associated with cognitive decline, other AD biomarkers, and imaging evidence of neurodegeneration. In this prospective case-control study, an ultrasensitive assay was used to measure plasma NFL concentration in 193 cognitively healthy controls, 197 patients with mild cognitive impairment (MCI), and 180 patients with AD dementia from the Alzheimer’s Disease Neuroimaging Initiative. The study dates were September 7, 2005, to February 13, 2012. The plasma NFL analysis was performed in September 2016. Associations were tested between plasma NFL and diagnosis, Aβ pathologic features, CSF biomarkers of neuronal injury, cognition, brain structure, and metabolism. Among 193 cognitively healthy controls, 197 patients with mild cognitive impairment, and 180 patients with AD with dementia, plasma NFL correlated with CSF NFL (Spearman ρ = 0.59, P < .001). Plasma NFL was increased in patients with MCI (mean, 42.8 ng/L) and patients with AD dementia (mean, 51.0 ng/L) compared with controls (mean, 34.7 ng/L) (P < .001) and had high diagnostic accuracy for patients with AD with dementia vs controls (area under the receiver operating characteristic curve, 0.87, which is comparable to established CSF biomarkers). Plasma NFL was particularly high in patients with MCI and patients with AD dementia with Aβ pathologic features. High plasma NFL correlated with poor cognition and AD-related atrophy (at baseline and longitudinally) and with brain hypometabolism (longitudinally). Plasma NFL is associated with AD diagnosis and with cognitive, biochemical, and imaging hallmarks of the disease. This finding implies a potential usefulness for plasma NFL as a noninvasive biomarker in AD. This case-control study compares patients with mild cognitive impairment, patients with AD dementia, and cognitively healthy patients to test whether plasma neurofilament light concentrations are increased in patients with AD and associated with cognitive decline, other AD biomarkers, and imaging evidence of neurodegeneration.
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影响因子：
9.9
作者：
Mattsson N;Zetterberg H;Janelidze S;Insel PS;Andreasson U;Stomrud E;Palmqvist S;Baker D;Tan Hehir CA;Jeromin A;Hanlon D;Song L;Shaw LM;Trojanowski JQ;Weiner MW;Hansson O;Blennow K;ADNI Investigators
通讯作者：
ADNI Investigators
DOI：
10.1007/978-3-642-02498-6_20
发表时间：
2009
期刊：
LECTURE NOTES IN ARTIFICIAL INTELLIGENCE
影响因子：
--
作者：
Schwarz, Christopher;Fletcher, Evan;DeCarli, Charles;Carmichael, Owen
通讯作者：
Carmichael, Owen
影响因子：
11.2
作者：
Landau, Susan M.;Mintun, Mark A.;Joshi, Abhinay D.;Koeppe, Robert A.;Petersen, Ronald C.;Aisen, Paul S.;Weiner, Michael W.;Jagust, William J.
通讯作者：
Jagust, William J.
影响因子：
5.3
作者：
Rojas JC;Karydas A;Bang J;Tsai RM;Blennow K;Liman V;Kramer JH;Rosen H;Miller BL;Zetterberg H;Boxer AL
通讯作者：
Boxer AL
影响因子：
29
作者：
Zetterberg H;Skillbäck T;Mattsson N;Trojanowski JQ;Portelius E;Shaw LM;Weiner MW;Blennow K;Alzheimer’s Disease Neuroimaging Initiative
通讯作者：
Alzheimer’s Disease Neuroimaging Initiative