TDP-43 protein in plasma may index TDP-43 brain pathology in Alzheimer's disease and frontotemporal lobar degeneration.
TDP-43 protein in plasma may index TDP-43 brain pathology in Alzheimer's disease and frontotemporal lobar degeneration.
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DOI：
10.1007/s00401-008-0389-8
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发表时间：
2008-08
影响因子：
12.7
通讯作者：
Mann DM
中科院分区：
文献类型：
--
作者：
Foulds P;McAuley E;Gibbons L;Davidson Y;Pickering-Brown SM;Neary D;Snowden JS;Allsop D;Mann DM
尸检研究表明，约55%的额颞叶变性（FTLD）患者和25%的阿尔茨海默病（AD）患者的大脑中存在TDP-43免疫反应性病理变化。使用ELISA，我们研究了与正常对照受试者相比，我们是否可以检测到FTLD和AD患者血浆中TDP-43的存在或增加的量。我们检测到升高的TDP-43蛋白在血浆中的FTLD与临床额颞叶痴呆（FTD）患者的46%和AD患者的22%，相比对照组的8%。血浆TDP-43水平升高的FTD和AD患者比例与尸检研究中已知脑内存在TDP-43病理变化的患者比例密切对应。因此，升高的TDP-43血浆水平可以指示脑内的TDP-43病理。血浆TDP-43水平可以是生物标志物，其可以提供能够鉴定生命期间神经退行性疾病中TDP-43脑病理学的存在的实验室测试。这可能有助于区分那些FTLD的情况下，泛素/TDP-43病理在他们的大脑与tau蛋白病变。血浆TDP-43水平作为一种预测性试验，在指导旨在预防或消除FTLD和AD脑中tau或TDP-43病理变化的治疗策略方面可能具有很大的实用价值。
Autopsy studies have shown that about 55% of patients with frontotemporal lobar degeneration (FTLD) and 25% of patients with Alzheimer’s disease (AD) harbour TDP-43 immunoreactive pathological changes in their brains. Using ELISA, we investigated whether we could detect the presence, or increased amounts, of TDP-43 in plasma of patients with FTLD and AD compared to normal control subjects. We detected elevated levels of TDP-43 protein in plasma of 46% patients with FTLD with clinical frontotemporal dementia (FTD) and 22% patients with AD, compared to 8% of control subjects. The proportions of patients with FTD and AD showing raised plasma TDP-43 levels correspond closely to those proportions known from autopsy studies to contain TDP-43 pathological changes in their brains. Raised TDP-43 plasma levels may thereby index TDP-43 pathology within the brain. Plasma TDP-43 levels may be a biomarker that can provide a laboratory test capable of identifying the presence of TDP-43 brain pathology in neurodegenerative disease during life. It may help to distinguish those cases of FTLD with ubiquitin/TDP-43 pathology in their brains from those with tauopathy. As a predictive test, plasma TDP-43 level may have great practical value in directing therapeutic strategies aimed at preventing or removing tau or TDP-43 pathological changes from the brain in FTLD and AD.
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