脑脊液淀粉样蛋白β42/40 比值在阿尔茨海默病与非阿尔茨海默病痴呆的鉴别诊断中的作用。

The cerebrospinal fluid amyloid beta42/40 ratio in the differentiation of Alzheimer's disease from non-Alzheimer's dementia.

机构信息

Department of Geriatric Medicine, 925, Radboud University Nijmegen Medical Centre, P.O. Box 9101, 6500 HB Nijmegen, The Netherlands.

出版信息

Curr Alzheimer Res. 2010 Aug;7(5):470-6. doi: 10.2174/156720510791383796.

DOI:10.2174/156720510791383796

PMID:20043812

Abstract

BACKGROUND

Amyloid beta(40) (Abeta(40)) is the most abundant Abeta peptide in the brain. The cerebrospinal fluid (CSF) level of Abeta(40) might therefore be considered to most closely reflect the total Abeta load in the brain. Both in Alzheimer's disease (AD) and in normal aging the Abeta load in the brain has a large inter-individual variability. Relating Abeta(42) to Abeta(40) levels might consequently provide a more valid measure for reflecting the change in Abeta metabolism in dementia patients than the CSF Abeta(42) concentrations alone. This measure may also improve differential diagnosis between AD and other dementia syndromes, such as vascular dementia (VaD), dementia with Lewy bodies (DLB), and frontotemporal dementia (FTD).

OBJECTIVE

To investigate the diagnostic value of the CSF Abeta(42)/Abeta(40) ratio in differentiating AD from controls, VaD, DLB and FTD.

METHODS

We analysed the CSF Abeta(42)/Abeta(40) ratio, phosphorylated tau(181) and total tau in 69 patients with AD, 26 patients with VaD, 16 patients with DLB, 27 patients with FTD, and 47 controls.

RESULTS

Mean Abeta(40) levels were 2850 pg/ml in VaD and 2830 pg/ml in DLB patients, both significantly lower than in AD patients (3698 pg/ml; p<0.01). Abeta(40) levels in AD patients were not significantly different from those in controls (4035 pg/ml; p=0.384). The Abeta(42)/Abeta(40) ratio was significantly lower in AD patients than in all other groups (p <0.001, ANCOVA). Differentiating AD from VaD, DLB and non-AD dementia improved when the Abeta(42)/Abeta(40) ratio was used instead of Abeta(42) concentrations alone (p<0.01) The Abeta(42)/Abeta(40) ratio performed equally well as the combination of Abeta(42), phosphorylated tau(181) and total tau in differentiating AD from FTD and non-AD dementia. The diagnostic performance of the latter combination was not improved when the Abeta(42)/Abeta(40) ratio was used instead of Abeta(42) alone.

CONCLUSION

The CSF Abeta42/Abeta40 ratio improves differentiation of AD patients from VaD, DLB and non-AD dementia patients, when compared to Abeta42 alone, and is a more easily interpretable alternative to the combination of Abeta42, p-tau and t-tau when differentiating AD from either FTD or non-AD dementia.

摘要

背景

β淀粉样蛋白 40（Abeta(40)）是大脑中含量最丰富的 Abeta 肽。因此，脑脊液（CSF）中的 Abeta(40) 水平可能最能反映大脑中的总 Abeta 负荷。在阿尔茨海默病（AD）和正常衰老中，大脑中的 Abeta 负荷具有很大的个体间变异性。因此，与 Abeta(42) 相比，Abeta(40) 水平可能为痴呆患者的 Abeta 代谢变化提供更有效的衡量标准，而不仅仅是 CSF Abeta(42) 浓度。这种衡量标准还可以改善 AD 与其他痴呆综合征（如血管性痴呆（VaD）、路易体痴呆（DLB）和额颞叶痴呆（FTD））之间的鉴别诊断。

目的

研究脑脊液 Abeta(42)/Abeta(40) 比值在区分 AD 与对照组、VaD、DLB 和 FTD 中的诊断价值。

方法

我们分析了 69 例 AD 患者、26 例 VaD 患者、16 例 DLB 患者、27 例 FTD 患者和 47 例对照组的 CSF Abeta(42)/Abeta(40) 比值、磷酸化 tau(181) 和总 tau。

结果

VaD 患者的 Abeta(40) 水平平均为 2850pg/ml，DLB 患者的 Abeta(40) 水平平均为 2830pg/ml，均明显低于 AD 患者（3698pg/ml；p<0.01）。AD 患者的 Abeta(40) 水平与对照组无显著差异（4035pg/ml；p=0.384）。AD 患者的 Abeta(42)/Abeta(40) 比值明显低于其他所有组（p<0.001，ANCOVA）。当使用 Abeta(42)/Abeta(40) 比值代替 Abeta(42) 浓度时，AD 与 VaD、DLB 和非 AD 痴呆的区分得到改善（p<0.01）。当使用 Abeta(42)/Abeta(40) 比值代替 Abeta(42) 时，Abeta(42)、磷酸化 tau(181) 和总 tau 的组合在区分 AD 与 FTD 和非 AD 痴呆方面同样有效。当使用 Abeta(42)/Abeta(40) 比值代替 Abeta(42) 时，后者组合的诊断性能并未得到改善。