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脑脊液生物标志物(磷酸化tau181、总tau、Aβ42 和 Aβ40)在阿尔茨海默病和路易体痴呆前驱期的诊断价值。

Diagnostic Value of Cerebrospinal Fluid Biomarkers (Phospho-Tau181, total-Tau, Aβ42, and Aβ40) in Prodromal Stage of Alzheimer's Disease and Dementia with Lewy Bodies.

机构信息

University Hospital of Strasbourg, Laboratory of Biochemistry and Molecular Biology, Strasbourg, France.

University of Strasbourg and CNRS, Laboratoire de Neurosciences Cognitives et Adaptatives (LNCA), UMR7364, Strasbourg, France.

出版信息

J Alzheimers Dis. 2016;51(4):1069-83. doi: 10.3233/JAD-150731.

DOI:10.3233/JAD-150731
PMID:26923009
Abstract

BACKGROUND

Dementia with Lewy bodies (DLB) symptoms are close to those of Alzheimer's disease (AD), and the differential diagnosis is difficult especially early in the disease. Unfortunately, AD biomarkers in cerebrospinal fluid (CSF), and more particularly Aβ1 - 42, appear to be altered in dementia with Lewy bodies (DLB). However, the level of these biomarkers has never been studied in the prodromal stage of the disease.

OBJECTIVE

To compare these biomarkers between DLB and AD, with a particular focus on the prodromal stage.

METHODS

A total of 166 CSF samples were collected at the memory clinic of Strasbourg. They were obtained from prodromal DLB (pro-DLB), DLB dementia, prodromal AD (pro-AD), and AD dementia patients, and elderly controls. Phospho-Tau181, total-Tau, Aβ42, and Aβ40 were measured in the CSF.

RESULTS

At the prodromal stage, contrary to AD patients, DLB patients' biomarker levels in the CSF were not altered. At the demented stage of DLB, Aβ42 levels were reduced as well as Aβ40 levels. Thus, the Aβ42/Aβ40 ratio remained unchanged between the prodromal and demented stages, contrary to what was observed in AD. Tau and Phospho-Tau181 levels were unaltered in DLB patients.

CONCLUSIONS

We have shown that at the prodromal stage the DLB patients had no pathological profile. Consequently, CSF AD biomarkers are extremely useful for differentiating AD from DLB patients particularly at this stage when the clinical diagnosis is difficult. Thus, these results open up new perspectives on the interpretation of AD biomarkers in DLB.

摘要

背景

路易体痴呆(DLB)的症状与阿尔茨海默病(AD)相似,鉴别诊断尤其在疾病早期较为困难。不幸的是,脑脊液(CSF)中的 AD 生物标志物,特别是 Aβ1-42,似乎在路易体痴呆(DLB)中发生改变。然而,这些生物标志物的水平在疾病的前驱期从未被研究过。

目的

比较 DLB 和 AD 患者的这些生物标志物,特别是在疾病前驱期。

方法

共收集了来自斯特拉斯堡记忆诊所的 166 例 CSF 样本。这些样本来自前驱期 DLB(pro-DLB)、DLB 痴呆、前驱期 AD(pro-AD)和 AD 痴呆患者以及老年对照组。测量 CSF 中的磷酸化 Tau181、总 Tau、Aβ42 和 Aβ40。

结果

在前驱期,与 AD 患者不同,DLB 患者的 CSF 生物标志物水平没有改变。在 DLB 的痴呆阶段,Aβ42 水平和 Aβ40 水平均降低。因此,与 AD 观察到的情况相反,Aβ42/Aβ40 比值在前驱期和痴呆期之间保持不变。DLB 患者的 Tau 和磷酸化 Tau181 水平没有改变。

结论

我们已经表明,在前驱期,DLB 患者没有病理性特征。因此,CSF AD 生物标志物对于区分 AD 和 DLB 患者非常有用,特别是在临床诊断困难的这个阶段。因此,这些结果为 DLB 中 AD 生物标志物的解释开辟了新的视角。

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