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用于早期和差异化阿尔茨海默病诊断的脑脊液生物标志物。

Cerebrospinal Fluid Biomarkers for Early and Differential Alzheimer's Disease Diagnosis.

机构信息

Reference Center for Biological Markers of Dementia (BIODEM), Institute Born-Bunge, University of Antwerp, Antwerp, Belgium.

Department of Neurology and Memory Clinic, Hospital Network Antwerp (ZNA) Middelheim and Hoge Beuken, Antwerp, Belgium.

出版信息

J Alzheimers Dis. 2018;62(3):1199-1209. doi: 10.3233/JAD-170680.


DOI:10.3233/JAD-170680
PMID:29562530
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC5870045/
Abstract

An accurate and early diagnosis of Alzheimer's disease (AD) is important to select optimal patient care and is critical in current clinical trials targeting core AD neuropathological features. The past decades, much progress has been made in the development and validation of cerebrospinal fluid (CSF) biomarkers for the biochemical diagnosis of AD, including standardization and harmonization of (pre-) analytical procedures. This has resulted in three core CSF biomarkers for AD diagnostics, namely the 42 amino acid long amyloid-beta peptide (Aβ1-42), total tau protein (T-tau), and tau phosphorylated at threonine 181 (P-tau181). These biomarkers have been incorporated into research diagnostic criteria for AD and have an added value in the (differential) diagnosis of AD and related disorders, including mixed pathologies, atypical presentations, and in case of ambiguous clinical dementia diagnoses. The implementation of the CSF Aβ1-42/Aβ1-40 ratio in the core biomarker panel will improve the biomarker analytical variability, and will also improve early and differential AD diagnosis through a more accurate reflection of pathology. Numerous biomarkers are being investigated for their added value to the core AD biomarkers, aiming at the AD core pathological features like the amyloid mismetabolism, tau pathology, or synaptic or neuronal degeneration. Others aim at non-AD neurodegenerative, vascular or inflammatory hallmarks. Biomarkers are essential for an accurate identification of preclinical AD in the context of clinical trials with potentially disease-modifying drugs. Therefore, a biomarker-based early diagnosis of AD offers great opportunities for preventive treatment development in the near future.

摘要

阿尔茨海默病(AD)的准确和早期诊断对于选择最佳患者护理非常重要,对于当前针对 AD 核心神经病理学特征的临床试验也至关重要。过去几十年,在开发和验证用于 AD 生化诊断的脑脊液(CSF)生物标志物方面取得了很大进展,包括(前)分析程序的标准化和协调。这导致了 AD 诊断的三个核心 CSF 生物标志物,即 42 个氨基酸长的淀粉样蛋白-β肽(Aβ1-42)、总tau 蛋白(T-tau)和在苏氨酸 181 处磷酸化的 tau(P-tau181)。这些生物标志物已被纳入 AD 的研究诊断标准,并在 AD 和相关疾病(包括混合病理、非典型表现以及在临床痴呆诊断不明确的情况下)的(鉴别)诊断中具有附加价值。在核心生物标志物组中实施 CSF Aβ1-42/Aβ1-40 比值将改善生物标志物分析变异性,并通过更准确地反映病理学,从而改善 AD 的早期和鉴别诊断。正在研究许多生物标志物以增加其对核心 AD 生物标志物的附加值,目的是针对 AD 的核心病理特征,如淀粉样蛋白代谢紊乱、tau 病理学、或突触或神经元退化。其他目标是针对非 AD 神经退行性、血管或炎症特征。生物标志物对于在具有潜在疾病修饰药物的临床试验中准确识别临床前 AD 非常重要。因此,基于生物标志物的 AD 早期诊断为未来不久的预防性治疗开发提供了巨大机会。

相似文献

[1]
Cerebrospinal Fluid Biomarkers for Early and Differential Alzheimer's Disease Diagnosis.

J Alzheimers Dis. 2018

[2]
Alzheimer's disease CSF biomarkers: clinical indications and rational use.

Acta Neurol Belg. 2017-9

[3]
Clinical indications for analysis of Alzheimer's disease CSF biomarkers.

Rev Neurol (Paris). 2013-9-6

[4]
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[5]
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[6]
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Alzheimers Dement. 2014-8-20

[7]
[Cerebrospinal fluid biomarkers of Alzheimer's disease in current clinical practice].

Rev Med Suisse. 2016-4-20

[8]
Association between Cerebrospinal Fluid Biomarkers for Alzheimer's Disease, APOE Genotypes and Auditory Verbal Learning Task in Subjective Cognitive Decline, Mild Cognitive Impairment, and Alzheimer's Disease.

J Alzheimers Dis. 2016-7-29

[9]
No added diagnostic value of non-phosphorylated tau fraction (p-tau) in CSF as a biomarker for differential dementia diagnosis.

Alzheimers Res Ther. 2017-7-14

[10]
Simultaneous analysis of cerebrospinal fluid biomarkers using microsphere-based xMAP multiplex technology for early detection of Alzheimer's disease.

Methods. 2012-4-6

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[8]
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本文引用的文献

[1]
Concordance Between Different Amyloid Immunoassays and Visual Amyloid Positron Emission Tomographic Assessment.

JAMA Neurol. 2017-12-1

[2]
The Cerebrospinal Fluid Aβ1-42/Aβ1-40 Ratio Improves Concordance with Amyloid-PET for Diagnosing Alzheimer's Disease in a Clinical Setting.

J Alzheimers Dis. 2017

[3]
Alzheimer's disease CSF biomarkers: clinical indications and rational use.

Acta Neurol Belg. 2017-9

[4]
No added diagnostic value of non-phosphorylated tau fraction (p-tau) in CSF as a biomarker for differential dementia diagnosis.

Alzheimers Res Ther. 2017-7-14

[5]
Biochemical markers in vascular cognitive impairment associated with subcortical small vessel disease - A consensus report.

BMC Neurol. 2017-5-23

[6]
Recommendations for cerebrospinal fluid Alzheimer's disease biomarkers in the diagnostic evaluation of mild cognitive impairment.

Alzheimers Dement. 2016-10-27

[7]
Recommendations for CSF AD biomarkers in the diagnostic evaluation of dementia.

Alzheimers Dement. 2016-10-27

[8]
How to handle adsorption of cerebrospinal fluid amyloid β (1-42) in laboratory practice? Identifying problematic handlings and resolving the issue by use of the Aβ/Aβ ratio.

Alzheimers Dement. 2017-2-21

[9]
Selecting Aβ isoforms for an Alzheimer's disease cerebrospinal fluid biomarker panel.

Biomark Med. 2017-2

[10]
Cerebrospinal Fluid Aβ42/40 Corresponds Better than Aβ42 to Amyloid PET in Alzheimer's Disease.

J Alzheimers Dis. 2017

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