Characterization of novel CSF Tau and ptau biomarkers for Alzheimer's disease.
Characterization of novel CSF Tau and ptau biomarkers for Alzheimer's disease.
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DOI：
10.1371/journal.pone.0076523
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发表时间：
2013
期刊：
影响因子：
3.7
通讯作者：
Albright CF
中科院分区：
文献类型：
--
作者：
Meredith JE Jr;Sankaranarayanan S;Guss V;Lanzetti AJ;Berisha F;Neely RJ;Slemmon JR;Portelius E;Zetterberg H;Blennow K;Soares H;Ahlijanian M;Albright CF
脑脊髓液（CSF）中Aβ42、tau和p181 tau是公认的阿尔茨海默病（AD）的生物标志物。大量研究表明，与年龄匹配的对照组相比，轻度至中度AD患者的CSF tau和p181 tau水平升高。此外，这些增加可能预测认知正常老年人的临床前AD。尽管它们作为生物标志物的重要性，但CSF tau和ptau的分子性质尚不清楚。在目前的研究中，反相高效液相色谱法用于富集和浓缩tau蛋白，然后进行蛋白质印迹分析。在合并的CSF中检测到tau的多个N-末端和中间结构域片段，表观大小范围为<20 kDa至~40 kDa。AD和对照样品中tau片段的模式相似。相反，未检测到全长tau和含C末端的片段。为了定量水平，开发了5种tau ELISA和3种ptau ELISA以检测蛋白质的不同重叠区域。使用20份AD和20份年龄匹配的对照CSF样品确定每种测定的区分潜力。在tau ELISA中，对含有N-末端序列的tau（氨基酸9-198（基于tau 441编号）和9-163）具有特异性的两种测定法在AD和对照样品之间表现出最显著的差异。相比之下，用对更C-末端区域（氨基酸159-335）具有特异性的ELISA未检测到CSF tau。用测量氨基酸159-p181和159-p231的ptau测定也观察到显著的区分。有趣的是，当在含有氨基酸9-p181的tau种类的背景下测量时，p181的辨别潜力降低。综上所述，这些结果表明CSF中的tau以一系列片段的形式存在，并且AD与对照的区分取决于测量的tau种类的子集。这些测定为研究CSF tau和ptau作为其他神经退行性疾病的生物标志物提供了新的工具。
Cerebral spinal fluid (CSF) Aβ42, tau and p181tau are widely accepted biomarkers of Alzheimer’s disease (AD). Numerous studies show that CSF tau and p181tau levels are elevated in mild-to-moderate AD compared to age-matched controls. In addition, these increases might predict preclinical AD in cognitively normal elderly. Despite their importance as biomarkers, the molecular nature of CSF tau and ptau is not known. In the current study, reverse-phase high performance liquid chromatography was used to enrich and concentrate tau prior to western-blot analysis. Multiple N-terminal and mid-domain fragments of tau were detected in pooled CSF with apparent sizes ranging from <20 kDa to ~40 kDa. The pattern of tau fragments in AD and control samples were similar. In contrast, full-length tau and C-terminal-containing fragments were not detected. To quantify levels, five tau ELISAs and three ptau ELISAs were developed to detect different overlapping regions of the protein. The discriminatory potential of each assay was determined using 20 AD and 20 age-matched control CSF samples. Of the tau ELISAs, the two assays specific for tau containing N-terminal sequences, amino acids 9-198 (numbering based on tau 441) and 9-163, exhibited the most significant differences between AD and control samples. In contrast, CSF tau was not detected with an ELISA specific for a more C-terminal region (amino acids 159-335). Significant discrimination was also observed with ptau assays measuring amino acids 159-p181 and 159-p231. Interestingly, the discriminatory potential of p181 was reduced when measured in the context of tau species containing amino acids 9-p181. Taken together, these results demonstrate that tau in CSF occurs as a series of fragments and that discrimination of AD from control is dependent on the subset of tau species measured. These assays provide novel tools to investigate CSF tau and ptau as biomarkers for other neurodegenerative diseases.
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影响因子：
9.9
作者：
Borroni, B.;Malinverno, M.;Padovani, A.
通讯作者：
Padovani, A.
DOI：
10.1016/s0140-6736(20)32205-4
发表时间：
2021-04-24
期刊：
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影响因子：
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作者：
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通讯作者：
van der Flier WM
影响因子：
9.9
作者：
Franz, G;Beer, R;Deisenhammer, F
通讯作者：
Deisenhammer, F
影响因子：
4.2
作者：
Bahl, Justyna Maria Czarna;Heegaard, Niels H. H.;Christiansen, Michael
通讯作者：
Christiansen, Michael
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