Semiquantitative proteomic analysis of human hippocampal tissues from Alzheimer's disease and age-matched control brains.
Semiquantitative proteomic analysis of human hippocampal tissues from Alzheimer's disease and age-matched control brains.
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DOI：
10.1186/1559-0275-10-5
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发表时间：
2013-05-01
影响因子：
3.8
通讯作者：
Diamandis EP
中科院分区：
文献类型：
--
作者：
Begcevic I;Kosanam H;Martínez-Morillo E;Dimitromanolakis A;Diamandis P;Kuzmanov U;Hazrati LN;Diamandis EP
阿尔茨海默病（AD）是影响65岁以上人群的最常见的痴呆症类型。阿尔茨海默病的特征是细胞外沉积物（即β淀粉样蛋白斑块）和细胞内神经原纤维缠结，这两者都是突触丧失和神经元细胞死亡的主要参与者。迄今为止，脑脊液中Tau蛋白和β片段1-42已被研究作为潜在的AD生物标志物。然而，迫切需要确定新的生物标志物，以在早期阶段捕获疾病并具有更好的特异性。海马组织的高通量蛋白质组学和通路分析提供了疾病相关蛋白和生物标志物候选物的宝贵来源，因为它代表了阿尔茨海默病最早受影响的大脑区域之一。在这项研究中，从对照组和AD脑组织中鉴定了2954个蛋白（1203个蛋白中至少有2个多肽）。总的来说，在AD中检测到204种蛋白质，在对照样品中检测到600种蛋白质。将阿尔茨海默病和对照组特异性蛋白与脑脊液（CSF）基于文献的蛋白质组进行比较，发现204个阿尔茨海默病相关蛋白中的40个和600个对照组相关蛋白中的106个也存在于脑脊液中。由于大多数这些蛋白是细胞外/分泌来源，我们认为它们是候选生物标志物的潜在来源，需要在脑脊液样本中进一步研究和验证。我们的半定量蛋白质组学分析提供了最大的人类海马蛋白质组数据库之一。阿尔茨海默病和控制相关蛋白的列表代表了一组可能参与阿尔茨海默病发病机制的蛋白质，也可以作为未来阿尔茨海默病诊断的生物标志物。
Alzheimer’s disease (AD) is the most common type of dementia affecting people over 65 years of age. The hallmarks of AD are the extracellular deposits known as amyloid β plaques and the intracellular neurofibrillary tangles, both of which are the principal players involved in synaptic loss and neuronal cell death. Tau protein and Aβ fragment 1–42 have been investigated so far in cerebrospinal fluid as a potential AD biomarkers. However, an urgent need to identify novel biomarkers which will capture disease in the early stages and with better specificity remains. High-throughput proteomic and pathway analysis of hippocampal tissue provides a valuable source of disease-related proteins and biomarker candidates, since it represents one of the earliest affected brain regions in AD. In this study 2954 proteins were identified (with at least 2 peptides for 1203 proteins) from both control and AD brain tissues. Overall, 204 proteins were exclusively detected in AD and 600 proteins in control samples. Comparing AD and control exclusive proteins with cerebrospinal fluid (CSF) literature-based proteome, 40 out of 204 AD related proteins and 106 out of 600 control related proteins were also present in CSF. As most of these proteins were extracellular/secretory origin, we consider them as a potential source of candidate biomarkers that need to be further studied and verified in CSF samples. Our semiquantitative proteomic analysis provides one of the largest human hippocampal proteome databases. The lists of AD and control related proteins represent a panel of proteins potentially involved in AD pathogenesis and could also serve as prospective AD diagnostic biomarkers.
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影响因子：
2.5
作者：
Kohnken, R;Buerger, K;Hampel, H
通讯作者：
Hampel, H
影响因子：
3.7
作者：
Schutzer SE;Liu T;Natelson BH;Angel TE;Schepmoes AA;Purvine SO;Hixson KK;Lipton MS;Camp DG;Coyle PK;Smith RD;Bergquist J
通讯作者：
Bergquist J
DOI：
10.1007/bf02815140
发表时间：
1995-12-01
期刊：
MOLECULAR AND CHEMICAL NEUROPATHOLOGY
影响因子：
--
作者：
Blennow, K;Wallin, A;Vanmechelen, E
通讯作者：
Vanmechelen, E
影响因子：
120.7
作者：
Sunderland, T;Linker, G;Cohen, RM
通讯作者：
Cohen, RM
影响因子：
64.5
作者：
Huang Y;Mucke L
通讯作者：
Mucke L