路易体痴呆和阿尔茨海默病患者脑脊液中α-突触核蛋白、β-淀粉样蛋白 42 和 tau 的差异水平。

Differential levels of alpha-synuclein, beta-amyloid42 and tau in CSF between patients with dementia with Lewy bodies and Alzheimer's disease.

机构信息

Department of Molecular Neuroscience, Brain Research Institute, Niigata University, Asahimachi 1-757, Chuo-ku, Niigata 951-8585, Japan.

出版信息

J Neurol Neurosurg Psychiatry. 2010 Jun;81(6):608-10. doi: 10.1136/jnnp.2009.197483.

DOI:10.1136/jnnp.2009.197483

PMID:20522869

Abstract

BACKGROUND

The clinical diagnosis of dementia with Lewy bodies (DLB) is made on the basis of consensus criteria; however, the sensitivity of the criteria is relatively low. There are no generally accepted biomarkers to distinguish DLB from other dementias. Here the utility of quantification of alpha-synuclein, beta-amyloid42 (Abeta42) and tau in the CSF of patients with DLB, Alzheimer's disease (AD) and other dementias was examined.

METHODS

86 patients were divided into three age and sex matched groups: DLB (n=34), AD (n=31) and other dementias (n=21). Two patients with alpha-synuclein gene (SNCA) duplication were also examined. Abeta and tau were quantified using an ELISA kit. A modified sandwich ELISA was developed which enables the sensitive quantification of CSF alpha-synuclein.

RESULTS

Total and phosphorylated tau levels as well as Abeta40/42 and tau/Abeta42 ratios were significantly higher in AD patients than in patients with DLB (p<0.01) and other dementias (p<0.01). CSF alpha-synuclein levels in DLB patients were significantly lower than those in patients with AD (p<0.05) and other dementias (p<0.01). CSF alpha-synuclein level correlated with the Abeta42 level in DLB patients (p=0.01, r=0.43). Two patients with SNCA duplication exhibited relatively low levels of CSF alpha-synuclein.

CONCLUSIONS

The study suggests that reduced levels of CSF alpha-synuclein in DLB may reflect the accumulation of alpha-synuclein with Lewy pathology in the brain and that quantification of CSF alpha-synuclein helps in the differentiation of DLB from AD and other dementias in combination with Abeta42 and tau analysis.

摘要

背景

路易体痴呆（DLB）的临床诊断基于共识标准；然而，这些标准的敏感性相对较低。目前还没有普遍接受的生物标志物来区分 DLB 与其他类型的痴呆。本研究旨在评估脑脊液中α-突触核蛋白、β-淀粉样蛋白 42（Abeta42）和 tau 在 DLB、阿尔茨海默病（AD）和其他类型痴呆患者中的诊断价值。

方法

将 86 名患者分为三组（每组 30 名患者，年龄和性别匹配）：DLB 组、AD 组和其他类型痴呆组。还检查了两名携带α-突触核蛋白基因（SNCA）重复的患者。使用 ELISA 试剂盒定量检测 Abeta 和 tau。开发了一种改良的夹心 ELISA 法，能够灵敏地定量检测脑脊液中的α-突触核蛋白。

结果

AD 患者的总 tau 和磷酸化 tau 水平以及 Abeta40/42 和 tau/Abeta42 比值明显高于 DLB 患者（p<0.01）和其他类型痴呆患者（p<0.01）。DLB 患者的脑脊液α-突触核蛋白水平明显低于 AD 患者（p<0.05）和其他类型痴呆患者（p<0.01）。DLB 患者的脑脊液α-突触核蛋白水平与 Abeta42 水平呈正相关（p=0.01，r=0.43）。两名携带 SNCA 重复的患者脑脊液α-突触核蛋白水平相对较低。