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与阿尔茨海默病相比,路易体痴呆中的脑脊液标志物

Cerebrospinal fluid markers in dementia with lewy bodies compared with Alzheimer disease.

作者信息

Gómez-Tortosa Estrella, Gonzalo Isabel, Fanjul Samira, Sainz Maria José, Cantarero Susana, Cemillán Carlos, Yébenes Justo García, del Ser Teodoro

机构信息

Department of Neurology, Fundación Jiménez Díaz, the Brain Bank for Neurological Research, Complutense University, Madrid, Spain.

出版信息

Arch Neurol. 2003 Sep;60(9):1218-22. doi: 10.1001/archneur.60.9.1218.

Abstract

BACKGROUND

Most patients with dementia with Lewy bodies (DLB) exhibit diffuse plaque-only pathology with rare neocortical neurofibrillary tangles (NFTs), as opposed to the widespread cortical neurofibrillary-tau involvement in Alzheimer disease (AD). Another pathological difference is the astrocytic and microglial inflammatory responses, including release of interleukins (ILs), around the neuritic plaques and NFTs in AD brains that are absent or much lower in DLB. We analyzed cerebrospinal fluid (CSF) markers that reflect the pathological differences between AD and DLB.

OBJECTIVE

To determine CSF concentrations of tau, beta-amyloid, IL-1beta, and IL-6 as potential diagnostic clues to distinguish between AD and DLB.

METHODS

We measured total tau, beta-amyloid1-42, IL-1beta, and IL-6 levels in CSF samples of 33 patients with probable AD without parkinsonism, 25 patients with all the core features of DLB, and 46 age-matched controls.

RESULTS

Patients with AD had significantly higher levels of tau protein than patients with DLB and controls (P<.001). The most efficient cutoff value provided 76% specificity to distinguish AD and DLB cases. Patients with AD and DLB had lower, but not significantly so, beta-amyloid levels than controls. The combination of tau and beta-amyloid levels provided the best sensitivity (84%) and specificity (79%) to differentiate AD vs controls but was worse than tau values alone in discriminating between AD and DLB. Beta-amyloid levels had the best correlation with disease progression in both AD and DLB (P =.01). There were no significant differences in IL-1beta levels among patients with AD, patients with DLB, and controls. Patients with AD and DLB showed slightly, but not significantly, higher IL-6 levels than controls.

CONCLUSIONS

The tau levels in CSF may contribute to the clinical distinction between AD and DLB. Beta-amyloid CSF levels are similar in both dementia disorders and reflect disease progression better than tau levels. Interleukin CSF concentrations do not distinguish between AD and DLB.

摘要

背景

与阿尔茨海默病(AD)中广泛的皮质神经原纤维缠结(NFTs)累及不同,大多数路易体痴呆(DLB)患者表现为仅存在弥漫性斑块病理改变,新皮质神经原纤维缠结罕见。另一个病理差异是AD脑内神经炎性斑块和NFTs周围的星形胶质细胞和小胶质细胞炎症反应,包括白细胞介素(ILs)的释放,而DLB中这种反应不存在或程度低得多。我们分析了反映AD和DLB病理差异的脑脊液(CSF)标志物。

目的

确定脑脊液中tau、β-淀粉样蛋白、IL-1β和IL-6的浓度,作为区分AD和DLB的潜在诊断线索。

方法

我们测量了33例无帕金森综合征的可能AD患者、25例具有DLB所有核心特征的患者以及46例年龄匹配对照的脑脊液样本中总tau、β-淀粉样蛋白1-42、IL-1β和IL-6的水平。

结果

AD患者的tau蛋白水平显著高于DLB患者和对照(P<0.001)。最有效的截断值区分AD和DLB病例的特异性为76%。AD和DLB患者的β-淀粉样蛋白水平低于对照,但差异不显著。tau和β-淀粉样蛋白水平的联合检测在区分AD与对照时提供了最佳的敏感性(84%)和特异性(79%),但在区分AD和DLB时不如单独的tau值。β-淀粉样蛋白水平与AD和DLB的疾病进展相关性最佳(P = 0.01)。AD患者、DLB患者和对照之间的IL-1β水平无显著差异。AD和DLB患者的IL-6水平略高于对照,但差异不显著。

结论

脑脊液中的tau水平可能有助于AD和DLB的临床鉴别。两种痴呆症中的脑脊液β-淀粉样蛋白水平相似,且比tau水平更能反映疾病进展。脑脊液白细胞介素浓度不能区分AD和DLB。

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