期刊
EMBO MOLECULAR MEDICINE
卷 8, 期 5, 页码 466-476出版社
WILEY
DOI: 10.15252/emmm.201506123
关键词
Alzheimer's disease; biomarkers; microglia; neurodegeneration; TREM2
资金
- European Research Council Under the European Union/ERC [321366-Amyloid]
- Deutsche Forschungsgemeinschaft (German Research Foundation) within the framework of the Munich Cluster for Systems Neurology [EXC 1010 SyNergy]
- Cure Alzheimer's Fund
- MetLife Foundation
- Swedish Research Council
- Torsten Soderberg Foundation at the Royal Swedish Academy of Sciences
- Knut and Alice Wallenberg Foundation
- Frimurarestiftelsen
- University of Antwerp
- Institute Born-Bunge
- Foundation for Alzheimer Research (SAO-FRA)
- Neurosearch Antwerp
- Research Foundation-Flanders (FWO)
- Agency for Innovation by Science and Technology (IWT)
- Interuniversity Attraction Poles (IAP) Program of the Belgian Science Policy Office
- Flemish Government Methusalem Excellence Program, Belgium
- Flanders Impulse Program on Networks for Dementia Research (VIND)
- EU/EFPIA Innovative Medicines Initiative Joint Undertaking (EMIF) [115372]
- Belgian Science Policy Office Interuniversity Attraction Poles Program
- Flanders Government Initiated Impulse Program on Networks for Dementia Research (VIND)
- Flemish government Initiated Methusalem Excellence Program
- University of Antwerp Research Fund, Belgium
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.
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