sTREM2 cerebrospinal fluid levels are a potential biomarker for microglia activity in early-stage Alzheimer's disease and associate with neuronal injury markers
Por:
Suarez-Calvet, M, Kleinberger, G, Caballero, MAA, Brendel, M, Rominger, A, Alcolea, D, Fortea, J, Lleo, A, Blesa, R, Gispert, JD, Sanchez-Valle, R, Antonell, A, Rami, L, Molinuevo, JL, Brosseron, F, Traschutz, A, Heneka, MT, Struyfs, H, Engelborghs, S, Sleegers, K, Van Broeckhoven, C, Zetterberg, H, Nellgard, B, Blennow, K, Crispin, A, Ewers, M, Haass, C
Publicada:
1 may 2016
Resumen:
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.
Filiaciones:
Suarez-Calvet, M:
Univ Munich, BioMed Ctr BMC, Biochem, Munich, Germany
German Ctr Neurodegenerat Dis DZNE Munich, Munich, Germany
Kleinberger, G:
Univ Munich, BioMed Ctr BMC, Biochem, Munich, Germany
Munich Cluster Syst Neurol SyNergy, Munich, Germany
Caballero, MAA:
Univ Munich, Klinikum Univ Munchen, Inst Stroke & Dementia Res, Munich, Germany
Brendel, M:
Univ Munich, Klinikum Univ Munchen, Dept Nucl Med, Munich, Germany
Rominger, A:
Munich Cluster Syst Neurol SyNergy, Munich, Germany
Univ Munich, Klinikum Univ Munchen, Dept Nucl Med, Munich, Germany
Alcolea, D:
Univ Autonoma Barcelona, Hosp Santa Creu & St Pau, Inst Invest Biomed, Dept Neurol, E-08193 Barcelona, Spain
CIBERNED, Ctr Networked Biomed Res Neurodegenerat Dis, Madrid, Spain
Fortea, J:
Univ Autonoma Barcelona, Hosp Santa Creu & St Pau, Inst Invest Biomed, Dept Neurol, E-08193 Barcelona, Spain
CIBERNED, Ctr Networked Biomed Res Neurodegenerat Dis, Madrid, Spain
Lleo, A:
Univ Autonoma Barcelona, Hosp Santa Creu & St Pau, Inst Invest Biomed, Dept Neurol, E-08193 Barcelona, Spain
CIBERNED, Ctr Networked Biomed Res Neurodegenerat Dis, Madrid, Spain
Blesa, R:
Univ Autonoma Barcelona, Hosp Santa Creu & St Pau, Inst Invest Biomed, Dept Neurol, E-08193 Barcelona, Spain
CIBERNED, Ctr Networked Biomed Res Neurodegenerat Dis, Madrid, Spain
Gispert, JD:
Pasqual Maragall Fdn, Barcelona Beta Brain Res Ctr, Clin & Neuroimaging Dept, Barcelona, Spain
Ctr Invest Biomed Red Bioingn Biomat & Nanomed CI, Barcelona, Spain
Sanchez-Valle, R:
ICN Hosp Clin & Univ, Neurol Serv, Alzheimers Dis & Other Cognit Disorders Unit, Barcelona, Spain
Inst Invest Biomed August Pi & Sunyer IDIBAPS, Barcelona, Spain
Antonell, A:
ICN Hosp Clin & Univ, Neurol Serv, Alzheimers Dis & Other Cognit Disorders Unit, Barcelona, Spain
Inst Invest Biomed August Pi & Sunyer IDIBAPS, Barcelona, Spain
Rami, L:
ICN Hosp Clin & Univ, Neurol Serv, Alzheimers Dis & Other Cognit Disorders Unit, Barcelona, Spain
Inst Invest Biomed August Pi & Sunyer IDIBAPS, Barcelona, Spain
Molinuevo, JL:
Pasqual Maragall Fdn, Barcelona Beta Brain Res Ctr, Clin & Neuroimaging Dept, Barcelona, Spain
Ctr Invest Biomed Red Bioingn Biomat & Nanomed CI, Barcelona, Spain
ICN Hosp Clin & Univ, Neurol Serv, Alzheimers Dis & Other Cognit Disorders Unit, Barcelona, Spain
Inst Invest Biomed August Pi & Sunyer IDIBAPS, Barcelona, Spain
Brosseron, F:
German Ctr Neurodegenerat Dis DZNE, Bonn, Germany
Traschutz, A:
Univ Klinikum Bonn, Dept Neurol, Bonn, Germany
Heneka, MT:
German Ctr Neurodegenerat Dis DZNE, Bonn, Germany
Univ Klinikum Bonn, Dept Neurol, Bonn, Germany
Struyfs, H:
Univ Antwerp, Inst Born Bunge, Lab Neurochem & Behav, Reference Ctr Biol Markers Dementia BIODEM, B-2020 Antwerp, Belgium
Hosp Network Antwerp ZNA Middelheim & Hoge Beuken, Dept Neurol, Antwerp, Belgium
Hosp Network Antwerp ZNA Middelheim & Hoge Beuken, Memory Clin, Antwerp, Belgium
Engelborghs, S:
Univ Antwerp, Inst Born Bunge, Lab Neurochem & Behav, Reference Ctr Biol Markers Dementia BIODEM, B-2020 Antwerp, Belgium
Hosp Network Antwerp ZNA Middelheim & Hoge Beuken, Dept Neurol, Antwerp, Belgium
Hosp Network Antwerp ZNA Middelheim & Hoge Beuken, Memory Clin, Antwerp, Belgium
Sleegers, K:
VIB, Dept Mol Genet, Neurodegenerat Brain Dis Grp, Antwerp, Belgium
Univ Antwerp, Inst Born Bunge, Neurogenet Lab, B-2020 Antwerp, Belgium
Van Broeckhoven, C:
VIB, Dept Mol Genet, Neurodegenerat Brain Dis Grp, Antwerp, Belgium
Univ Antwerp, Inst Born Bunge, Neurogenet Lab, B-2020 Antwerp, Belgium
Zetterberg, H:
Univ Gothenburg, Sahlgrenska Acad, Inst Neurosci & Physiol, Clin Neurochem Lab, Molndal, Sweden
UCL Inst Neurol, Reta Lila Weston Labs, London, England
UCL Inst Neurol, Dept Mol Neurosci, London, England
Nellgard, B:
Gothenburg Univ, Sahlgrenska Acad, Inst Clin Sci, Dept Anaesthesiol & Intens Care, Gothenburg, Sweden
Blennow, K:
Univ Gothenburg, Sahlgrenska Acad, Inst Neurosci & Physiol, Clin Neurochem Lab, Molndal, Sweden
Crispin, A:
Inst Med Informat Biometry & Epidemiol, Munich, Germany
Ewers, M:
Univ Munich, Klinikum Univ Munchen, Inst Stroke & Dementia Res, Munich, Germany
Haass, C:
Univ Munich, BioMed Ctr BMC, Biochem, Munich, Germany
German Ctr Neurodegenerat Dis DZNE Munich, Munich, Germany
Munich Cluster Syst Neurol SyNergy, Munich, Germany
Gold, Green Published
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