• 文献检索
  • 文档翻译
  • 深度研究
  • 学术资讯
  • Suppr Zotero 插件Zotero 插件
  • 邀请有礼
  • 套餐&价格
  • 历史记录
应用&插件
Suppr Zotero 插件Zotero 插件浏览器插件Mac 客户端Windows 客户端微信小程序
定价
高级版会员购买积分包购买API积分包
服务
文献检索文档翻译深度研究API 文档MCP 服务
关于我们
关于 Suppr公司介绍联系我们用户协议隐私条款
关注我们

Suppr 超能文献

核心技术专利:CN118964589B侵权必究
粤ICP备2023148730 号-1Suppr @ 2026

文献检索

告别复杂PubMed语法,用中文像聊天一样搜索,搜遍4000万医学文献。AI智能推荐,让科研检索更轻松。

立即免费搜索

文件翻译

保留排版,准确专业,支持PDF/Word/PPT等文件格式,支持 12+语言互译。

免费翻译文档

深度研究

AI帮你快速写综述,25分钟生成高质量综述,智能提取关键信息,辅助科研写作。

立即免费体验

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.

DOI:10.1186/s40035-019-0168-6
PMID:31467673
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC6712703/
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。

相似文献

1
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.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。
Transl Neurodegener. 2019 Aug 27;8:25. doi: 10.1186/s40035-019-0168-6. eCollection 2019.
2
Alzheimer's cerebrospinal biomarkers from Lumipulse fully automated immunoassay: concordance with amyloid-beta PET and manual immunoassay in Koreans : CSF AD biomarkers measured by Lumipulse in Koreans.基于 Lumipulse 全自动免疫分析的阿尔茨海默病脑脊液生物标志物:与韩国人群中淀粉样蛋白-β PET 和手工免疫分析的一致性:韩国人群中通过 Lumipulse 测量的 CSF AD 生物标志物。
Alzheimers Res Ther. 2021 Jan 12;13(1):22. doi: 10.1186/s13195-020-00767-3.
3
Cerebrospinal Fluid Biomarkers for the Diagnosis and Classification of Alzheimer's Disease Spectrum.用于阿尔茨海默病谱系诊断和分类的脑脊液生物标志物。
J Korean Med Sci. 2020 Nov 16;35(44):e361. doi: 10.3346/jkms.2020.35.e361.
4
Concordance between brain F-FDG PET and cerebrospinal fluid biomarkers in diagnosing Alzheimer's disease.脑 F-FDG PET 与脑脊液生物标志物在诊断阿尔茨海默病中的一致性。
Rev Esp Med Nucl Imagen Mol (Engl Ed). 2018 Jan-Feb;37(1):3-8. doi: 10.1016/j.remn.2017.05.003. Epub 2017 Jun 20.
5
CSF and blood Kallikrein-8: a promising early biomarker for Alzheimer's disease.脑脊液和血液 Kallikrein-8:阿尔茨海默病有前景的早期生物标志物。
J Neurol Neurosurg Psychiatry. 2020 Jan;91(1):40-48. doi: 10.1136/jnnp-2019-321073. Epub 2019 Aug 1.
6
Stage-dependent agreement between cerebrospinal fluid proteins and FDG-PET findings in Alzheimer's disease.阿尔茨海默病患者脑脊液蛋白与 FDG-PET 检查结果的阶段相关性。
Curr Alzheimer Res. 2012 Feb;9(2):241-7. doi: 10.2174/156720512799361592.
7
Unravelling the Association Between Amyloid-PET and Cerebrospinal Fluid Biomarkers in the Alzheimer's Disease Spectrum: Who Really Deserves an A+?揭开阿尔茨海默病谱中淀粉样蛋白-PET 与脑脊液生物标志物之间的关联:谁真正值得获得 A+?
J Alzheimers Dis. 2022;85(3):1009-1020. doi: 10.3233/JAD-210593.
8
Clinic-Based Validation of Cerebrospinal Fluid Biomarkers with Florbetapir PET for Diagnosis of Dementia.基于临床的脑脊液生物标志物与氟代脱氧葡萄糖 PET 对痴呆症的诊断验证。
J Alzheimers Dis. 2018;61(1):135-143. doi: 10.3233/JAD-170753.
9
Oligomeric forms of amyloid-β protein in plasma as a potential blood-based biomarker for Alzheimer's disease.血浆中淀粉样β蛋白的寡聚形式作为阿尔茨海默病潜在的基于血液的生物标志物。
Alzheimers Res Ther. 2017 Dec 15;9(1):98. doi: 10.1186/s13195-017-0324-0.
10
Analysis of Cerebrospinal Fluid and [11C]PIB PET Biomarkers for Alzheimer's Disease with Updated Protocols.采用更新方案对阿尔茨海默病的脑脊液和[11C]PIB正电子发射断层显像生物标志物进行分析。
J Alzheimers Dis. 2016 May 6;52(4):1403-13. doi: 10.3233/JAD-160143.

引用本文的文献

1
Divergent actions of physiological and pathological amyloid-β on synapses in live human brain slice cultures.生理和病理β-淀粉样蛋白对活人脑切片培养物中突触的不同作用。
Nat Commun. 2025 Apr 30;16(1):3753. doi: 10.1038/s41467-025-58879-z.
2
Characterizing plasma and cerebrospinal fluid biomarkers relevant to neurodegeneration in captive olive baboons (Papio anubis).表征圈养橄榄狒狒(Papio anubis)中与神经退行性变相关的血浆和脑脊液生物标志物。
PLoS One. 2025 Feb 13;20(2):e0318173. doi: 10.1371/journal.pone.0318173. eCollection 2025.
3
CD4-Derived Double-Negative T Cells Ameliorate Alzheimer's Disease-Like Phenotypes in the 5×FAD Mouse Model.

本文引用的文献

1
NIA-AA Research Framework: Toward a biological definition of Alzheimer's disease.NIA-AA 研究框架:迈向阿尔茨海默病的生物学定义。
Alzheimers Dement. 2018 Apr;14(4):535-562. doi: 10.1016/j.jalz.2018.02.018.
2
Higher levels of kallikrein-8 in female brain may increase the risk for Alzheimer's disease.女性大脑中 Kallikrein-8 水平升高可能会增加患阿尔茨海默病的风险。
Brain Pathol. 2018 Nov;28(6):947-964. doi: 10.1111/bpa.12599. Epub 2018 Apr 10.
3
Assessment of kallikrein 6 as a cross-sectional and longitudinal biomarker for Alzheimer's disease.
CD4衍生的双阴性T细胞改善5×FAD小鼠模型中的阿尔茨海默病样表型。
CNS Neurosci Ther. 2025 Jan;31(1):e70187. doi: 10.1111/cns.70187.
4
Plasma proteomics identify biomarkers and undulating changes of brain aging.血浆蛋白质组学可识别脑衰老的生物标志物及波动变化。
Nat Aging. 2025 Jan;5(1):99-112. doi: 10.1038/s43587-024-00753-6. Epub 2024 Dec 9.
5
Mediation Analysis with Multiple Exposures and Multiple Mediators.多暴露和多中介的中介分析。
Stat Med. 2024 Nov 10;43(25):4887-4898. doi: 10.1002/sim.10215. Epub 2024 Sep 9.
6
Elecsys Cerebrospinal Fluid Immunoassays Accurately Detect Alzheimer's Disease Regardless of Concomitant Small Vessel Disease.Elecsys 脑脊液免疫分析能够准确检测阿尔茨海默病,而与小血管病无关。
J Alzheimers Dis. 2023;93(4):1537-1549. doi: 10.3233/JAD-221187.
7
Persistent Depletion of Neuroprotective Factors Accompanies Neuroinflammatory, Neurodegenerative, and Vascular Remodeling Spectra in Serum Three Months after Non-Emergent Cardiac Surgery.非急诊心脏手术后三个月,血清中神经保护因子的持续消耗伴随着神经炎症、神经退行性变和血管重塑谱。
Biomedicines. 2022 Sep 22;10(10):2364. doi: 10.3390/biomedicines10102364.
8
Multimodal data integration via mediation analysis with high-dimensional exposures and mediators.通过高维暴露和中介的中介分析进行多模态数据整合。
Hum Brain Mapp. 2022 Jun 1;43(8):2519-2533. doi: 10.1002/hbm.25800. Epub 2022 Feb 7.
9
Proteomics and functional study reveal kallikrein-6 enhances communicating hydrocephalus.蛋白质组学与功能研究表明激肽释放酶-6会加重交通性脑积水。
Clin Proteomics. 2021 Dec 16;18(1):30. doi: 10.1186/s12014-021-09335-9.
10
KLK8 promotes the proliferation and metastasis of colorectal cancer via the activation of EMT associated with PAR1.KLK8 通过激活与 PAR1 相关的 EMT 促进结直肠癌的增殖和转移。
Cell Death Dis. 2021 Sep 22;12(10):860. doi: 10.1038/s41419-021-04149-x.
评估激肽释放酶 6 作为阿尔茨海默病的横断面和纵向生物标志物。
Alzheimers Res Ther. 2018 Jan 29;10(1):9. doi: 10.1186/s13195-018-0336-4.
4
Kallikrein 6 secreted by oligodendrocytes regulates the progression of experimental autoimmune encephalomyelitis.少突胶质细胞分泌的激肽释放酶 6 调节实验性自身免疫性脑脊髓炎的进展。
Glia. 2018 Feb;66(2):359-378. doi: 10.1002/glia.23249. Epub 2017 Oct 31.
5
Neuroinflammation in Neurodegenerative Disorders-a Review.神经退行性疾病中的神经炎症——综述。
Curr Neurol Neurosci Rep. 2017 Mar;17(3):25. doi: 10.1007/s11910-017-0733-2.
6
Structural basis for the Zn2+ inhibition of the zymogen-like kallikrein-related peptidase 10.锌离子对类酶原激肽释放酶相关肽酶10抑制作用的结构基础
Biol Chem. 2016 Dec 1;397(12):1251-1264. doi: 10.1515/hsz-2016-0205.
7
A/T/N: An unbiased descriptive classification scheme for Alzheimer disease biomarkers.A/T/N:阿尔茨海默病生物标志物的无偏描述性分类方案。
Neurology. 2016 Aug 2;87(5):539-47. doi: 10.1212/WNL.0000000000002923. Epub 2016 Jul 1.
8
Kallikrein-8 inhibition attenuates Alzheimer's disease pathology in mice.激肽释放酶-8 抑制可减轻小鼠的阿尔茨海默病病理。
Alzheimers Dement. 2016 Dec;12(12):1273-1287. doi: 10.1016/j.jalz.2016.05.006. Epub 2016 Jun 18.
9
Identification of brain-enriched proteins in the cerebrospinal fluid proteome by LC-MS/MS profiling and mining of the Human Protein Atlas.通过液相色谱-串联质谱分析和挖掘人类蛋白质图谱来鉴定脑脊液蛋白质组中脑富集蛋白。
Clin Proteomics. 2016 May 15;13:11. doi: 10.1186/s12014-016-9111-3. eCollection 2016.
10
The role of human kallikrein 6, clusterin and adiponectin as potential blood biomarkers of dementia.人激肽释放酶6、簇集素和脂联素作为痴呆潜在血液生物标志物的作用。
Clin Biochem. 2016 Feb;49(3):213-8. doi: 10.1016/j.clinbiochem.2015.10.014. Epub 2015 Oct 26.