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验证 Tau Thr231 磷酸化 CSF ELISA 原型作为阿尔茨海默病潜在生物标志物的研究。

Validation of a prototype tau Thr231 phosphorylation CSF ELISA as a potential biomarker for Alzheimer's disease.

机构信息

Department of Psychiatry and Psychotherapy, University Medical Center Goettingen (UMG), Georg-August University, Von-Siebold-Str. 5, 37075, Goettingen, Germany.

Medical Science Department, iBiMED, University of Aveiro, Aveiro, Portugal.

出版信息

J Neural Transm (Vienna). 2019 Mar;126(3):339-348. doi: 10.1007/s00702-019-01982-5. Epub 2019 Feb 14.

DOI:10.1007/s00702-019-01982-5
PMID:30767082
Abstract

Alzheimer's disease (AD) is a progressive neurodegenerative disorder characterized by the presence of extracellular amyloid plaques (senile plaques) and intracellular neurofibrillary tangles formed by hyperphosphorylated tau protein. This process leads to neuronal degradation and neuronal death. Phosphorylation of tau protein at threonine 231 (p-tau231) has been shown to be characteristic in post-mortem brain tissue of patients with AD and it can be sensitively detected in cerebrospinal fluid (CSF). Therefore, it may serve as a biomarker to support the diagnosis of AD. In this study, we analysed how well p-tau231 could differentiate between patients suffering from dementia either due or not due to AD by a sandwich enzyme immunoassay. CSF p-tau231 was significantly higher in patients with dementia due to AD than in those with dementia due to other causes. In addition, we studied different factors affecting p-tau231 levels in CSF. We found that apolipoprotein E genotype influences p-tau231 CSF levels. Gender and age did not affect p-tau231 levels in CSF. Our findings indicate that p-tau231 levels in CSF can be a valuable marker for the clinical diagnosis of AD.

摘要

阿尔茨海默病(AD)是一种进行性神经退行性疾病,其特征是存在细胞外淀粉样斑块(老年斑)和由过度磷酸化的 tau 蛋白形成的细胞内神经原纤维缠结。这一过程导致神经元降解和神经元死亡。在 AD 患者的死后脑组织中,tau 蛋白在苏氨酸 231 位的磷酸化(p-tau231)已被证明具有特征性,并且可以在脑脊液(CSF)中灵敏地检测到。因此,它可以作为支持 AD 诊断的生物标志物。在这项研究中,我们通过夹心酶免疫测定分析了 p-tau231 如何区分因 AD 或其他原因导致痴呆的患者。AD 导致的痴呆患者的 CSF p-tau231 明显高于其他原因导致的痴呆患者。此外,我们研究了影响 CSF 中 p-tau231 水平的不同因素。我们发现载脂蛋白 E 基因型影响 CSF 中 p-tau231 的水平。性别和年龄并不影响 CSF 中的 p-tau231 水平。我们的研究结果表明,CSF 中的 p-tau231 水平可以作为 AD 临床诊断的有价值的标志物。

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