sTREM2 cerebrospinal fluid levels are a potential biomarker for microglia activity in early-stage Alzheimer's disease and associate with neuronal injury markers

被引：391

作者：

Suarez-Calvet, Marc ^{[1
,2
]}

Kleinberger, Gernot ^{[1
,3
]}

Caballero, Miguel Angel Araque ^{[4
]}

Brendel, Matthias ^{[5
]}

Rominger, Axel ^{[3
,5
]}

Alcolea, Daniel ^{[6
,7
]}

Fortea, Juan ^{[6
,7
]}

Lleo, Alberto ^{[6
,7
]}

Blesa, Rafael ^{[6
,7
]}

Gispert, Juan Domingo ^{[8
,9
]}

Sanchez-Valle, Raquel ^{[10
,11
]}

Antonell, Anna ^{[10
,11
]}

Rami, Lorena ^{[10
,11
]}

Molinuevo, Jose L. ^{[8
,9
,10
,11
]}

Brosseron, Frederic ^{[12
]}

Traschuetz, Andreas ^{[13
]}

Heneka, Michael T. ^{[12
,13
]}

Struyfs, Hanne ^{[14
,15
,16
]}

Engelborghs, Sebastiaan ^{[14
,15
,16
]}

Sleegers, Kristel ^{[17
,18
]}

Van Broeckhoven, Christine ^{[17
,18
]}

Zetterberg, Henrik ^{[19
,20
,21
]}

Nellgard, Bengt ^{[22
]}

Blennow, Kaj ^{[19
]}

Crispin, Alexander ^{[23
]}

Ewers, Michael ^{[4
]}

Haass, Christian ^{[1
,2
,3
]}

机构：

[1] Univ Munich, BioMed Ctr BMC, Biochem, Munich, Germany

[2] German Ctr Neurodegenerat Dis DZNE Munich, Munich, Germany

[3] Munich Cluster Syst Neurol SyNergy, Munich, Germany

[4] Univ Munich, Klinikum Univ Munchen, Inst Stroke & Dementia Res, Munich, Germany

[5] Univ Munich, Klinikum Univ Munchen, Dept Nucl Med, Munich, Germany

[6] Univ Autonoma Barcelona, Hosp Santa Creu & St Pau, Inst Invest Biomed, Dept Neurol, E-08193 Barcelona, Spain

[7] CIBERNED, Ctr Networked Biomed Res Neurodegenerat Dis, Madrid, Spain

[8] Pasqual Maragall Fdn, Barcelona Beta Brain Res Ctr, Clin & Neuroimaging Dept, Barcelona, Spain

[9] Ctr Invest Biomed Red Bioingn Biomat & Nanomed CI, Barcelona, Spain

[10] ICN Hosp Clin & Univ, Neurol Serv, Alzheimers Dis & Other Cognit Disorders Unit, Barcelona, Spain

[11] Inst Invest Biomed August Pi & Sunyer IDIBAPs, Barcelona, Spain

[12] German Ctr Neurodegenerat Dis DZNE, Bonn, Germany

[13] Univ Klinikum Bonn, Dept Neurol, Bonn, Germany

[14] Univ Antwerp, Inst Born Bunge, Lab Neurochem & Behav, Reference Ctr Biol Markers Dementia BIODEM, B-2020 Antwerp, Belgium

[15] Hosp Network Antwerp ZNA Middelheim & Hoge Beuken, Dept Neurol, Antwerp, Belgium

[16] Hosp Network Antwerp ZNA Middelheim & Hoge Beuken, Memory Clin, Antwerp, Belgium

[17] VIB, Dept Mol Genet, Neurodegenerat Brain Dis Grp, Antwerp, Belgium

[18] Univ Antwerp, Inst Born Bunge, Neurogenet Lab, B-2020 Antwerp, Belgium

[19] Univ Gothenburg, Sahlgrenska Acad, Inst Neurosci & Physiol, Clin Neurochem Lab, Molndal, Sweden

[20] UCL Inst Neurol, Reta Lila Weston Labs, London, England

[21] UCL Inst Neurol, Dept Mol Neurosci, London, England

[22] Gothenburg Univ, Sahlgrenska Acad, Inst Clin Sci, Dept Anaesthesiol & Intens Care, Gothenburg, Sweden

[23] Inst Med Informat Biometry & Epidemiol, Munich, Germany

来源：

EMBO MOLECULAR MEDICINE | 2016年 / 8卷 / 05期

基金：

瑞典研究理事会; 欧洲研究理事会;

关键词：

Alzheimer's disease; biomarkers; microglia; neurodegeneration; TREM2; MILD COGNITIVE IMPAIRMENT; DIAGNOSTIC GUIDELINES; NATIONAL INSTITUTE; FRONTOTEMPORAL DEMENTIA; CONSENSUS PAPER; MYELOID CELLS-2; TREM2; RECOMMENDATIONS; WORKGROUPS; EXPRESSION;

D O I：

10.15252/emmm.201506123

中图分类号：

R-3 [医学研究方法]; R3 [基础医学];

学科分类号：

1001 ;

摘要：

TREM2 is an innate immune receptor expressed on the surface of microglia. Loss-of-function mutations of TREM2 are associated with increased risk of Alzheimer's disease (AD). TREM2 is a type-1 protein with an ectodomain that is proteolytically cleaved and released into the extracellular space as a soluble variant (sTREM2), which can be measured in the cerebrospinal fluid (CSF). In this cross-sectional multicenter study, we investigated whether CSF levels of sTREM2 are changed during the clinical course of AD, and in cognitively normal individuals with suspected non-AD pathology (SNAP). CSF sTREM2 levels were higher in mild cognitive impairment due to AD than in all other AD groups and controls. SNAP individuals also had significantly increased CSF sTREM2 compared to controls. Moreover, increased CSF sTREM2 levels were associated with higher CSF total tau and phospho-tau(181P), which are markers of neuronal degeneration and tau pathology. Our data demonstrate that CSF sTREM2 levels are increased in the early symptomatic phase of AD, probably reflecting a corresponding change of the microglia activation status in response to neuronal degeneration.

引用

页码：466 / 476

页数：11

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