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阿尔茨海默病脑脊液生物标志物在常规临床环境中的应用。

Alzheimer CSF biomarkers in routine clinical setting.

机构信息

Clinical Center, Clinique du Colombier, Limoges, France.

出版信息

Acta Neurol Scand. 2012 Jun;125(6):416-23. doi: 10.1111/j.1600-0404.2011.01592.x. Epub 2011 Sep 28.

Abstract

OBJECTIVES

Our work was aimed to evaluate Alzheimer's disease diagnosis improvement using cerebrospinal fluid biomarkers (CSF) in neurological daily practice.

MATERIALS AND METHODS

For this purpose, 150 patients clinically and neurochemically classified as having AD or cognitive impairment with or without other dementia type were included in the study. The following CSF peptides were studied, blindly to the clinical diagnosis: beta-amyloid(1-42) peptide (Aβ(1-42)), Tau (T-tau), threonine-181 hyperphosphorylated tau protein (P-tau(181)), and beta-amyloid(1-40) peptide (Aβ(1-40)). From these measurements, Innotest® Amyloid Tau Index (IATI) was calculated for each patient.

RESULTS

This assessment allowed to separate 83 biochemical profiles of AD and 67 non-Alzheimer's disease (non-AD), both AD and non-AD categories match with clinical data amounting to 73% and 90%, respectively. Among mild cognitive impairment (MCI) patients, CSF biomarkers led to discriminate those who are likely to be AD. We devoted a special section to Aβ(1-40) which is not a routine parameter but can help to confirm a pathological amyloid process as Aβ(1-42)/Aβ(1-40) ratio underlining the real decline of the Aβ(1-42).

CONCLUSIONS

The interest of biomarkers and their ability to solve awkward cases were carefully noticed all the more when a discrepancy between clinical and CSF biological data was involved. The final proposed algorithm allowed to identify pathogenic forms of AD according to the prevailing role of hyperphosphorylated tau or amyloid beta peptide.

摘要

目的

本研究旨在评估在神经科日常实践中使用脑脊液生物标志物(CSF)改善阿尔茨海默病(AD)的诊断。

材料与方法

为此,我们纳入了 150 例临床和神经化学分类为 AD 或认知障碍(伴有或不伴有其他类型痴呆)的患者。我们对以下 CSF 肽进行了研究,这些研究是盲法进行的,与临床诊断无关:β-淀粉样蛋白(1-42)肽(Aβ(1-42))、Tau(T-tau)、苏氨酸 181 位磷酸化 Tau 蛋白(P-tau(181))和β-淀粉样蛋白(1-40)肽(Aβ(1-40))。根据这些测量结果,我们计算了每位患者的 Innotest®淀粉样蛋白 Tau 指数(IATI)。

结果

该评估可将 83 例 AD 生化特征和 67 例非 AD 特征区分开来,AD 和非 AD 分类与临床数据匹配,分别为 73%和 90%。在轻度认知障碍(MCI)患者中,CSF 生物标志物可用于区分那些可能患有 AD 的患者。我们专门讨论了 Aβ(1-40),它不是常规参数,但可以帮助确认病理性淀粉样蛋白过程,因为 Aβ(1-42)/Aβ(1-40)比值突出了 Aβ(1-42)的实际下降。

结论

当临床和 CSF 生物学数据之间存在差异时,生物标志物的重要性及其解决棘手病例的能力得到了特别关注。最终提出的算法根据过度磷酸化 Tau 或淀粉样蛋白β肽的主导作用,可识别 AD 的致病性形式。

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