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阿尔茨海默病患者脑脊液中α-突触核蛋白水平升高:与tau 蛋白水平的相关性。

Increased CSF α-synuclein levels in Alzheimer's disease: correlation with tau levels.

机构信息

Reference Center for Biological Markers of Dementia (BIODEM), Laboratory of Neurochemistry and Behavior, Institute Born-Bunge, University of Antwerp, Antwerp, Belgium.

Innogenetics NV (Miraca/Fujirebio Group), Ghent, Belgium.

出版信息

Alzheimers Dement. 2014 Oct;10(5 Suppl):S290-8. doi: 10.1016/j.jalz.2013.10.004. Epub 2014 Jan 15.

DOI:10.1016/j.jalz.2013.10.004
PMID:24439167
Abstract

BACKGROUND

Given the difficult clinical differential diagnosis between Alzheimer's disease (AD) and dementia with Lewy bodies (DLB), growing interest resulted in research on α-synuclein as a potential cerebrospinal fluid biomarker (CSF) for synucleinopathies.

METHODS

CSF α-synuclein-140 concentrations were determined by a prototype xMAP™ bead-based assay (Innogenetics NV, Belgium). In addition, CSF amyloid β1-42 (Aβ1-42), total tau (T-tau), and phosphorylated tau (P-tau181P) levels were determined.

RESULTS

CSF α-synuclein levels were higher in AD patients as compared with cognitively healthy controls (P=.019) and patients with synucleinopathies (P<.001). CSF α-synuclein levels were correlated with T-tau (P<.001) and P-tau181P (P<.001) levels in autopsy-confirmed AD patients. A diagnostic algorithm using α-synuclein and P-tau181P discriminated neuropathologically confirmed AD from DLB patients, resulting in sensitivity and specificity values of 85% and 81%, respectively.

CONCLUSION

Because CSF α-synuclein levels were significantly higher in AD as compared with synucleinopathies, α-synuclein might have a value as a biomarker for differential dementia diagnosis.

摘要

背景

鉴于阿尔茨海默病(AD)与路易体痴呆(DLB)之间临床鉴别诊断困难,因此人们对α-突触核蛋白作为潜在的突触核蛋白病脑脊液生物标志物(CSF)的研究兴趣日益浓厚。

方法

采用 Innogenetics NV(比利时)的 xMAP™ 珠基分析测定法( prototype xMAP™ bead-based assay)测定 CSFα-突触核蛋白-140 浓度。此外,还测定了 CSF 淀粉样蛋白β1-42(Aβ1-42)、总tau(T-tau)和磷酸化 tau(P-tau181P)水平。

结果

与认知健康对照者(P=.019)和其他突触核蛋白病患者(P<.001)相比,AD 患者的 CSFα-突触核蛋白水平更高。CSFα-突触核蛋白水平与尸检确诊 AD 患者的 T-tau(P<.001)和 P-tau181P(P<.001)水平相关。采用α-突触核蛋白和 P-tau181P 的诊断算法可区分经神经病理学确诊的 AD 与 DLB 患者,其敏感性和特异性值分别为 85%和 81%。

结论

由于 AD 患者的 CSFα-突触核蛋白水平明显高于突触核蛋白病患者,因此α-突触核蛋白可能作为鉴别性痴呆诊断的生物标志物具有一定价值。

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