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脑脊液淀粉样蛋白 β38 作为路易体痴呆的新型诊断标志物。

CSF amyloid β38 as a novel diagnostic marker for dementia with Lewy bodies.

机构信息

Department of Old Age Psychiatry, Psychiatric Clinic, Stavanger University Hospital, Stavanger, Norway.

出版信息

J Neurol Neurosurg Psychiatry. 2011 Feb;82(2):160-4. doi: 10.1136/jnnp.2009.199398. Epub 2010 Nov 3.

DOI:10.1136/jnnp.2009.199398
PMID:21047883
Abstract

BACKGROUND

The clinical distinction between Alzheimer's disease (AD) and dementia with Lewy bodies (DLB) is sometimes difficult, particularly in mild cases. Although CSF markers such as amyloid β42 (Aβ42) and P-tau can distinguish between AD and normal controls, their ability to distinguish between AD and DLB is not adequate.

OBJECTIVE

This study aims to investigate whether CSF markers, in particular levels of Aβ38, can differentiate between mild AD and DLB.

METHODS

85 individuals were included after standardised diagnostic procedures: 30 diagnosed as probable AD, 23 probable DLB, 20 probable Parkinson's disease dementia and 12 non-demented control subjects. CSF levels of Aβ38, Aβ40 and Aβ42 were determined using commercially available ultra-sensitive multi-array kit assay (MSD) for human Aβ peptides. Total tau (T-tau) and phosphorylated tau (P-tau) were analysed using ELISA (Innotest). In addition, combinations (Aβ42/Aβ38, Aβ42/Aβ40, Aβ42/P-tau and Aβ42/Aβ38/P-tau) were assessed.

RESULTS

Significant between group differences were found for all CSF measures, and all except Aβ40, Aβ42 and Aβ42/P-tau differed between AD and DLB. The Aβ42/Aβ38 ratio was the measure that best discriminated between AD and DLB (AUC 0.765; p<0.005), with a sensitivity of 78% and a specificity of 67%.

CONCLUSION

This study suggests that the level of Aβ38 can potentially contribute in the diagnostic distinction between AD and DLB when combined with Aβ42. Single measures had low diagnostic accuracy, suggesting that developing a panel of markers is the most promising strategy. Studies with independent and larger samples and a priori cut-offs are needed to test this hypothesis.

摘要

背景

阿尔茨海默病(AD)和路易体痴呆(DLB)的临床鉴别有时较为困难,尤其是在轻度病例中。尽管脑脊液标志物如 Aβ42(Aβ42)和 P-tau 可以区分 AD 和正常对照,但它们区分 AD 和 DLB 的能力还不够。

目的

本研究旨在探讨脑脊液标志物,特别是 Aβ38 的水平,是否可以区分轻度 AD 和 DLB。

方法

经过标准诊断程序后,共纳入 85 名个体:30 名被诊断为可能的 AD,23 名可能的 DLB,20 名可能的帕金森病痴呆和 12 名非痴呆对照。使用商业上可获得的超敏多阵列试剂盒(MSD)测定人 Aβ 肽的 CSF 水平的 Aβ38、Aβ40 和 Aβ42。使用 ELISA(Innotest)分析总 tau(T-tau)和磷酸化 tau(P-tau)。此外,还评估了组合(Aβ42/Aβ38、Aβ42/Aβ40、Aβ42/P-tau 和 Aβ42/Aβ38/P-tau)。

结果

所有 CSF 指标在组间均存在显著差异,除 Aβ40、Aβ42 和 Aβ42/P-tau 外,AD 和 DLB 之间的所有指标均存在差异。Aβ42/Aβ38 比值是区分 AD 和 DLB 的最佳指标(AUC 0.765;p<0.005),其敏感性为 78%,特异性为 67%。

结论

本研究表明,当与 Aβ42 结合使用时,Aβ38 的水平可能有助于 AD 和 DLB 的诊断区分。单一指标的诊断准确性较低,表明开发标志物组合是最有前途的策略。需要进行具有独立和更大样本量以及先验截止值的研究来验证这一假设。

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