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Soluble TREM2 ameliorates pathological phenotypes by modulating microglial functions in an Alzheimer’s disease model
- Source :
- Nature Communications, Vol 10, Iss 1, Pp 1-16 (2019), Nature Communications
- Publication Year :
- 2019
- Publisher :
- Nature Publishing Group, 2019.
-
Abstract
- Triggering receptor expressed on myeloid cells 2 (TREM2) is a microglial surface receptor genetically linked to the risk for Alzheimer’s disease (AD). A proteolytic product, soluble TREM2 (sTREM2), is abundant in the cerebrospinal fluid and its levels positively correlate with neuronal injury markers. To gain insights into the pathological roles of sTREM2, we studied sTREM2 in the brain of 5xFAD mice, a model of AD, by direct stereotaxic injection of recombinant sTREM2 protein or by adeno-associated virus (AAV)-mediated expression. We found that sTREM2 reduces amyloid plaque load and rescues functional deficits of spatial memory and long-term potentiation. Importantly, sTREM2 enhances microglial proliferation, migration, clustering in the vicinity of amyloid plaques and the uptake and degradation of Aβ. Depletion of microglia abolishes the neuroprotective effects of sTREM2. Our study demonstrates a protective role of sTREM2 against amyloid pathology and related toxicity and suggests that increasing sTREM2 can be explored for AD therapy.<br />TREM2 is a genetic risk factor for Alzheimer’s disease, and soluble TREM2 (sTREM2) in the CSF correlates with AD progression. Here the authors study the role of sTREM2 in a mouse model of Alzheimer’s disease, and find it reduces amyloid accumulation and increases the numbers of plaque-associated microglia which correlates with improved behavioural function in the mice.
- Subjects :
- Male
0301 basic medicine
Long-Term Potentiation
Neuroimmunology
Gene Expression
General Physics and Astronomy
Plaque, Amyloid
02 engineering and technology
Stereotaxic Techniques
Mice
Cerebrospinal fluid
Cell Movement
Receptors, Immunologic
Receptor
lcsh:Science
Spatial Memory
Neurons
Membrane Glycoproteins
Multidisciplinary
Microglia
Brain
Long-term potentiation
Dependovirus
Alzheimer's disease
021001 nanoscience & nanotechnology
3. Good health
Cell biology
Phenotype
medicine.anatomical_structure
Female
0210 nano-technology
Science
Recombinant Fusion Proteins
Genetic Vectors
Green Fluorescent Proteins
Primary Cell Culture
Biology
Neuroprotection
Article
General Biochemistry, Genetics and Molecular Biology
03 medical and health sciences
Alzheimer Disease
medicine
Animals
Humans
Author Correction
Cell Proliferation
Injections, Intraventricular
Amyloid beta-Peptides
TREM2
General Chemistry
Peptide Fragments
Disease Models, Animal
030104 developmental biology
Animals, Newborn
Cell culture
Proteolysis
Stereotaxic technique
lcsh:Q
Subjects
Details
- Language :
- English
- ISSN :
- 20411723
- Volume :
- 10
- Issue :
- 1
- Database :
- OpenAIRE
- Journal :
- Nature Communications
- Accession number :
- edsair.doi.dedup.....26a6d212b5a3080721f3a9c96980b554