脑脊液 Tau 蛋白水平升高的痴呆的鉴别诊断

Differential Diagnosis of Dementia with High Levels of Cerebrospinal Fluid Tau Protein.

作者信息

Grangeon Lou, Paquet Claire, Bombois Stephanie, Quillard-Muraine Muriel, Martinaud Olivier, Bourre Bertrand, Lefaucheur Romain, Nicolas Gaël, Dumurgier Julien, Gerardin Emmanuel, Jan Mary, Laplanche Jean-Louis, Peoc'h Katell, Hugon Jacques, Pasquier Florence, Maltête David, Hannequin Didier, Wallon David

机构信息

Department of Neurology, Rouen University Hospital, Rouen, France.

CMRR Paris Nord AP-HP, Groupe Hospitalier Lariboisière Fernand-Widal Saint-Louis, INSERM, U942, Université Paris Diderot, Sorbonne Paris Cité, UMRS 942, Paris, France.

出版信息

J Alzheimers Dis. 2016;51(3):905-13. doi: 10.3233/JAD-151111.

DOI:10.3233/JAD-151111

PMID:26890785

Abstract

BACKGROUND

Total Tau concentration in cerebrospinal fluid (CSF) is widely used as a biomarker in the diagnosis of neurodegenerative process primarily in Alzheimer's disease (AD). A particularly high Tau level may indicate AD but may also be associated with Creutzfeldt-Jakob disease (CJD). In such situations little is known about the distribution of differential diagnoses.

OBJECTIVE

Our study aimed to describe the different diagnoses encountered in clinical practice for patients with dementia and CSF Tau levels over 1000 pg/ml. We studied the p-Tau/Tau ratio to specify its ability to distinguish AD from CJD.

METHODS

Patients (n = 202) with CSF Tau levels over 1000 pg/ml were recruited in three memory clinics in France. All diagnoses were made using the same diagnostic procedure and criteria.

RESULTS

Patients were diagnosed with AD (n = 148, 73.2%), mixed dementia (n = 38, 18.8%), CJD, vascular dementia (n = 4, 2.0% for each), Lewy body dementia, and frontotemporal dementia (n = 3, 1.5% for each). Dispersion of CSF Tau levels clearly showed an overlap between all diagnoses. Using the p-Tau/Tau ratio suggestive of CJD (<0.075), all CJD patients were correctly categorized and only two AD patients were miscategorized. This ratio was highly associated with CJD compared to AD (p < 0.0001).

CONCLUSION

Our study showed that in clinical practice, extremely high CSF Tau levels are mainly related to diagnosis of AD. CJD patients represent a minority. Our results support a sequential interpretation algorithm for CSF biomarkers in dementia. High CSF Tau levels should alert clinicians to check the p-Tau/Tau ratio to consider a probable diagnosis of CJD.

摘要

背景

脑脊液（CSF）中的总 Tau 浓度被广泛用作神经退行性疾病（主要是阿尔茨海默病（AD））诊断中的生物标志物。Tau 水平特别高可能提示 AD，但也可能与克雅氏病（CJD）有关。在这种情况下，关于鉴别诊断的分布情况知之甚少。

目的

我们的研究旨在描述临床实践中痴呆患者且脑脊液 Tau 水平超过 1000 pg/ml 时遇到的不同诊断。我们研究了磷酸化 Tau（p-Tau）/Tau 比值以明确其区分 AD 和 CJD 的能力。

方法

在法国的三家记忆诊所招募了脑脊液 Tau 水平超过 1000 pg/ml 的患者（n = 202）。所有诊断均采用相同的诊断程序和标准。

结果

患者被诊断为 AD（n = 148，73.2%）、混合性痴呆（n = 38，18.8%）、CJD、血管性痴呆（每种 n = 4，2.0%）、路易体痴呆和额颞叶痴呆（每种 n = 3，1.5%）。脑脊液 Tau 水平的离散度清楚地表明所有诊断之间存在重叠。使用提示 CJD 的 p-Tau/Tau 比值（<0.075），所有 CJD 患者均被正确分类，只有两名 AD 患者被错误分类。与 AD 相比，该比值与 CJD 高度相关（p < 0.0001）。