SNAP-25 is a promising novel cerebrospinal fluid biomarker for synapse degeneration in Alzheimer's disease.
SNAP-25 is a promising novel cerebrospinal fluid biomarker for synapse degeneration in Alzheimer's disease.
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DOI：
10.1186/1750-1326-9-53
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发表时间：
2014-11-23
影响因子：
15.1
通讯作者：
Öhrfelt A
中科院分区：
文献类型：
--
作者：
Brinkmalm A;Brinkmalm G;Honer WG;Frölich L;Hausner L;Minthon L;Hansson O;Wallin A;Zetterberg H;Blennow K;Öhrfelt A
突触变性是阿尔茨海默病的早期致病事件，与认知障碍和疾病进展相关。反映突触完整性的脑脊液生物标志物将是直接监测患者突触变性的极有价值的工具。我们之前的研究表明，突触蛋白如synaptotagmin和突触体相关蛋白25 （SNAP-25）可以在脑脊液的混合样本中检测到，但是这些检测方法对单个样本不够敏感。我们报道了一种研究突触病理的新策略，通过亲和纯化和质谱法测量脑脊液中突触前蛋白SNAP-25的水平。通过将这种新的亲和质谱策略应用于三个独立的患者队列，SNAP-25作为阿尔茨海默病突触完整性脑脊液生物标志物的价值首次得到评估。在三个独立的队列中，我们发现阿尔茨海默病患者的脑脊液SNAP-25片段水平明显较高，即使在非常早期的阶段也是如此。脑脊液SNAP-25与对照区分阿尔茨海默病的曲线下面积为0.901 （P < 0.0001）。我们开发了一种灵敏的方法来分析单个CSF样品中的SNAP-25水平，据我们所知，这在以前是不可能的。我们的研究结果支持这样一种观点，即突触生物标志物可能是早期诊断、疾病进展评估和治疗试验中监测药物效应的重要工具。本文的在线版本（doi:10.1186/1750-1326-9-53）包含补充材料，可供授权用户使用。
Synaptic degeneration is an early pathogenic event in Alzheimer’s disease, associated with cognitive impairment and disease progression. Cerebrospinal fluid biomarkers reflecting synaptic integrity would be highly valuable tools to monitor synaptic degeneration directly in patients. We previously showed that synaptic proteins such as synaptotagmin and synaptosomal-associated protein 25 (SNAP-25) could be detected in pooled samples of cerebrospinal fluid, however these assays were not sensitive enough for individual samples. We report a new strategy to study synaptic pathology by using affinity purification and mass spectrometry to measure the levels of the presynaptic protein SNAP-25 in cerebrospinal fluid. By applying this novel affinity mass spectrometry strategy on three separate cohorts of patients, the value of SNAP-25 as a cerebrospinal fluid biomarker for synaptic integrity in Alzheimer’s disease was assessed for the first time. We found significantly higher levels of cerebrospinal fluid SNAP-25 fragments in Alzheimer’s disease, even in the very early stages, in three separate cohorts. Cerebrospinal fluid SNAP-25 differentiated Alzheimer’s disease from controls with area under the curve of 0.901 (P < 0.0001). We developed a sensitive method to analyze SNAP-25 levels in individual CSF samples that to our knowledge was not possible previously. Our results support the notion that synaptic biomarkers may be important tools for early diagnosis, assessment of disease progression, and to monitor drug effects in treatment trials. The online version of this article (doi:10.1186/1750-1326-9-53) contains supplementary material, which is available to authorized users.
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通过使用在线纳米型-si-ftiCR-MS方法，鉴定人脑组织中新型α-突触核蛋白同工型。
影响因子：
4.4
作者：
Ohrfelt, Annika;Zetterberg, Henrik;Andersson, Kerstin;Persson, Rita;Secic, Dzemila;Brinkmalm, Gunnar;Wallin, Anders;Mulugeta, Ezra;Francis, Paul T.;Vanmechelen, Eugeen;Aarsland, Dag;Ballard, Clive;Blennow, Kaj;Westman-Brinkmalm, Ann
通讯作者：
Westman-Brinkmalm, Ann
DOI：
10.1007/bf02815094
发表时间：
1996-02-01
期刊：
MOLECULAR AND CHEMICAL NEUROPATHOLOGY
影响因子：
--
作者：
Davidsson, P;Jahn, R;Blennow, K
通讯作者：
Blennow, K
影响因子：
2.3
作者：
Brinkmalm, Gunnar;Portelius, Erik;Brinkmalm, Ann
通讯作者：
Brinkmalm, Ann
影响因子：
4
作者：
Guerini, Franca Rosa;Agliardi, Cristina;Clerici, Mario
通讯作者：
Clerici, Mario
影响因子：
3.3
作者：
Honer, WG;Falkai, P;Trimble, WS
通讯作者：
Trimble, WS