Peptide fingerprinting of Alzheimer's disease in cerebrospinal fluid: identification and prospective evaluation of new synaptic biomarkers.
Peptide fingerprinting of Alzheimer's disease in cerebrospinal fluid: identification and prospective evaluation of new synaptic biomarkers.
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DOI：
10.1371/journal.pone.0026540
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发表时间：
2011
期刊：
影响因子：
3.7
通讯作者：
Wiedemann K
中科院分区：
文献类型：
--
作者：
Jahn H;Wittke S;Zürbig P;Raedler TJ;Arlt S;Kellmann M;Mullen W;Eichenlaub M;Mischak H;Wiedemann K
如今，痴呆症在疾病进程较晚阶段才被诊断出来。未来的治疗必须在疾病发展过程中更早启动，这就需要新的诊断工具以避免残疾。本研究的目的是利用毛细管电泳 - 质谱联用技术（CE - MS）开发一种用于阿尔茨海默病（AD）鉴别诊断以及识别新生物标志物的新方法，并评估AD早期诊断的潜力。
我们使用了一所大学医院记忆门诊的159名患有神经退行性疾病的门诊患者以及17名认知健康对照者的脑脊液（CSF），以创建痴呆症的差异肽模式，并在一个自然前瞻性患者样本中，针对标准诊断标准对AD诊断的敏感性和特异性进行前瞻性盲法比较。主要的观察指标是新方法与标准诊断程序相比的敏感性和特异性，以及对AD新的潜在生物标志物的识别。CE - MS被用于可靠地检测脑脊液中的1104种低分子量肽。由临床确诊的散发性阿尔茨海默病、额颞叶痴呆患者以及认知健康对照者组成的训练集，使得建立用于AD诊断的鉴别性生物标志物模式成为可能。这种模式在轻度认知障碍（MCI）患者中就已经可以检测到。在一个前瞻性患者样本（n = 100）中对AD模式进行了测试，AD诊断的敏感性为87%，特异性为83%。在同一组样本中，使用脑脊液中β - 淀粉样蛋白1 - 42、总tau蛋白和磷酸化181 - tau蛋白的测量值，AD诊断的敏感性为88%，特异性为67%。对鉴别性生物标志物的序列分析确定了一些突触蛋白的片段，如proSAAS、载脂蛋白J、神经分泌蛋白VGF、磷酸受纳蛋白和嗜铬粒蛋白A。
该方法可以利用特定的肽指纹图谱对各种痴呆症进行早期鉴别诊断，并识别患有MCI的患者中初期的AD。所识别的生物标志物为其在AD诊断中的应用提供了表面效度。
Today, dementias are diagnosed late in the course of disease. Future treatments have to start earlier in the disease process to avoid disability requiring new diagnostic tools. The objective of this study is to develop a new method for the differential diagnosis and identification of new biomarkers of Alzheimer's disease (AD) using capillary-electrophoresis coupled to mass-spectrometry (CE-MS) and to assess the potential of early diagnosis of AD. Cerebrospinal fluid (CSF) of 159 out-patients of a memory-clinic at a University Hospital suffering from neurodegenerative disorders and 17 cognitively-healthy controls was used to create differential peptide pattern for dementias and prospective blinded-comparison of sensitivity and specificity for AD diagnosis against the Criterion standard in a naturalistic prospective sample of patients. Sensitivity and specificity of the new method compared to standard diagnostic procedures and identification of new putative biomarkers for AD was the main outcome measure. CE-MS was used to reliably detect 1104 low-molecular-weight peptides in CSF. Training-sets of patients with clinically secured sporadic Alzheimer's disease, frontotemporal dementia, and cognitively healthy controls allowed establishing discriminative biomarker pattern for diagnosis of AD. This pattern was already detectable in patients with mild cognitive impairment (MCI). The AD-pattern was tested in a prospective sample of patients (n = 100) and AD was diagnosed with a sensitivity of 87% and a specificity of 83%. Using CSF measurements of beta-amyloid1-42, total-tau, and phospho181-tau, AD-diagnosis had a sensitivity of 88% and a specificity of 67% in the same sample. Sequence analysis of the discriminating biomarkers identified fragments of synaptic proteins like proSAAS, apolipoprotein J, neurosecretory protein VGF, phospholemman, and chromogranin A. The method may allow early differential diagnosis of various dementias using specific peptide fingerprints and identification of incipient AD in patients suffering from MCI. Identified biomarkers facilitate face validity for the use in AD diagnosis.
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影响因子：
30.8
作者：
Harold, Denise;Abraham, Richard;Hollingworth, Paul;Sims, Rebecca;Gerrish, Amy;Hamshere, Marian L.;Pahwa, Jaspreet Singh;Moskvina, Valentina;Dowzell, Kimberley;Williams, Amy;Jones, Nicola;Thomas, Charlene;Stretton, Alexandra;Morgan, Angharad R.;Lovestone, Simon;Powell, John;Proitsi, Petroula;Lupton, Michelle K.;Brayne, Carol;Rubinsztein, David C.;Gill, Michael;Lawlor, Brian;Lynch, Aoibhinn;Morgan, Kevin;Brown, Kristelle S.;Passmore, Peter A.;Craig, David;McGuinness, Bernadette;Todd, Stephen;Holmes, Clive;Mann, David;Smith, A. David;Love, Seth;Kehoe, Patrick G.;Hardy, John;Mead, Simon;Fox, Nick;Rossor, Martin;Collinge, John;Maier, Wolfgang;Jessen, Frank;Schuermann, Britta;van den Bussche, Hendrik;Heuser, Isabella;Kornhuber, Johannes;Wiltfang, Jens;Dichgans, Martin;Froelich, Lutz;Hampel, Harald;Huell, Michael;Rujescu, Dan;Goate, Alison M.;Kauwe, John S. K.;Cruchaga, Carlos;Nowotny, Petra;Morris, John C.;Mayo, Kevin;Sleegers, Kristel;Bettens, Karolien;Engelborghs, Sebastiaan;De Deyn, Peter P.;Van Broeckhoven, Christine;Livingston, Gill;Bass, Nicholas J.;Gurling, Hugh;McQuillin, Andrew;Gwilliam, Rhian;Deloukas, Panagiotis;Al-Chalabi, Ammar;Shaw, Christopher E.;Tsolaki, Magda;Singleton, Andrew B.;Guerreiro, Rita;Muehleisen, Thomas W.;Noethen, Markus M.;Moebus, Susanne;Joeckel, Karl-Heinz;Klopp, Norman;Wichmann, H-Erich;Carrasquillo, Minerva M.;Pankratz, V. Shane;Younkin, Steven G.;Holmans, Peter A.;O'Donovan, Michael;Owen, Michael J.;Williams, Julie
通讯作者：
Williams, Julie
影响因子：
10.5
作者：
Bullock, R
通讯作者：
Bullock, R
影响因子：
7
作者：
Good, David M.;Zuerbig, Petra;Schmitt-Kopplin, Philippe
通讯作者：
Schmitt-Kopplin, Philippe
DOI：
10.1159/000106963
发表时间：
1995-11-01
期刊：
DEMENTIA
影响因子：
--
作者：
BLENNOW, K;DAVIDSSON, P;EKMAN, R
通讯作者：
EKMAN, R
影响因子：
7.4
作者：
Chalmers, MJ;Mackay, CL;Marshall, AG
通讯作者：
Marshall, AG