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激肽释放酶相关肽酶6和10在阿尔茨海默病患者的脑脊液中升高,并与脑脊液总tau蛋白和氟代脱氧葡萄糖正电子发射断层扫描相关。

Kallikrein-related peptidases 6 and 10 are elevated in cerebrospinal fluid of patients with Alzheimer's disease and associated with CSF-TAU and FDG-PET.

作者信息

Goldhardt Oliver, Warnhoff Inanna, Yakushev Igor, Begcevic Ilijana, Förstl Hans, Magdolen Viktor, Soosaipillai Antoninus, Diamandis Eleftherios, Alexopoulos Panagiotis, Grimmer Timo

机构信息

1Department of Psychiatry and Psychotherapy, Klinikum rechts der Isar, Technical University of Munich, School of Medicine, Ismaninger Str. 22, 81675 Munich, Germany.

2Department of Nuclear Medicine, TUM-NIC, Klinikum rechts der Isar, Technical University of Munich, School of Medicine, Ismaninger Str. 22, 81675 Munich, Germany.

出版信息

Transl Neurodegener. 2019 Aug 27;8:25. doi: 10.1186/s40035-019-0168-6. eCollection 2019.

Abstract

BACKGROUND

Alterations in the expression of human kallikrein-related peptidases (KLKs) have been described in patients with Alzheimer's disease (AD). We elucidated the suitability of KLK6, KLK8 and KLK10 to distinguish AD from NC and explored associations with established AD biomarkers.

METHODS

KLK levels in cerebrospinal fluid (CSF), as determined by ELISA, were compared between 32 AD patients stratified to A/T/(N) system with evidence for amyloid pathology and of 23 normal controls with normal AD biomarkers. Associations between KLK levels and clinical severity, CSF and positron emission tomography (PET) based AD biomarkers were tested for.

RESULTS

Levels of KLK6 and KLK10 were significantly increased in AD. KLK6 differed significantly between AD A+/T+/N+ and AD A+/T-/N+ or NC with an AUC of 0.922. CSF pTau and tTau levels were significantly associated with KLK6 in AD.

CONCLUSIONS

KLK6 deserves further investigations as a potential biomarker of Tau pathology in AD.

摘要

背景

在阿尔茨海默病(AD)患者中,已发现人组织激肽释放酶相关肽酶(KLKs)的表达存在改变。我们阐明了KLK6、KLK8和KLK10区分AD与正常对照(NC)的适用性,并探讨了其与已确立的AD生物标志物的相关性。

方法

通过酶联免疫吸附测定(ELISA)测定32例根据A/T/(N)系统分层且有淀粉样蛋白病理学证据的AD患者和23例AD生物标志物正常的正常对照者脑脊液(CSF)中的KLK水平。检测KLK水平与临床严重程度、基于CSF和正电子发射断层扫描(PET)的AD生物标志物之间的相关性。

结果

AD患者中KLK6和KLK10水平显著升高。AD A+/T+/N+与AD A+/T-/N+或NC之间的KLK6差异显著,曲线下面积(AUC)为0.922。AD患者CSF中磷酸化tau蛋白(pTau)和总tau蛋白(tTau)水平与KLK6显著相关。

结论

KLK6作为AD中Tau病理学的潜在生物标志物值得进一步研究。

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