Reduced TREM2 activation in microglia of patients with Alzheimer's disease

Reduced TREM2 activation in microglia of patients with Alzheimer’s disease

Loss-of-function variants of triggering receptor expressed on myeloid cells 2 (TREM2) enhance the chance of creating Alzheimer’s illness (AD). The mechanism via which TREM2 contributes to the illness (TREM2 activation vs inactivation) is basically unknown.
Right here, we analyzed adjustments in a gene set downstream of TREM2 to find out whether or not TREM2 signaling is modified by AD development. We generated an anti-human TREM2 agonistic antibody and outlined TREM2 activation when it comes to the downstream expression adjustments induced by this antibody in microglia developed from human induced pluripotent stem cells (iPSC).
Differentially expressed genes (DEGs) following TREM2 activation have been in contrast with the gene set extracted from microglial single nuclear RNA sequencing information of sufferers with AD, utilizing gene set enrichment evaluation.
We remoted an anti-TREM2-specific agonistic antibody, Hyb87, from anti-human TREM2 antibodies generated utilizing binding and agonism assays, which helped us determine 300 upregulated and 251 downregulated DEGs.
Pathway enrichment evaluation recommended that TREM2 activation could also be related to Th2-related pathways. TREM2 activation was decrease in AD microglia than in microglia from wholesome topics or sufferers with delicate cognitive impairment. TREM2 activation additionally confirmed a big unfavorable correlation with illness development.
Pathway enrichment evaluation of DEGs managed by TREM2 exercise indicated that TREM2 activation in AD could result in anti-apoptotic signaling, immune response, and cytoskeletal adjustments within the microglia.
We confirmed that TREM2 activation decreases with AD development, in assist of a protecting function of TREM2 activation in AD. As well as, the agonistic anti-TREM2 antibody can be utilized to determine TREM2 activation state in AD microglia.

Established Beta Amyloid Pathology Is Unaffected by TREM2 Elevation in Reactive Microglia in an Alzheimer’s Illness Mouse Mannequin

A number of genetic research have recognized a uncommon variant of triggering receptor expressed on myeloid cells 2 (TREM2) as a danger issue for Alzheimer’s illness (AD). Nonetheless, findings on the results of TREM2 on Aβ deposition are fairly inconsistent in animal research, requiring additional investigation.
On this research, we investigated whether or not elevation of TREM2 mitigates Aβ pathology in TgCRND8 mice. We discovered that peripheral nerve damage resulted in a sturdy elevation of TREM2 solely in reactive microglia within the ipsilateral spinal wire of aged TgCRND8 mice on the age of 20 months.
TREM2 expression appeared on day 1 post-injury and the upregulation was maintained for no less than 28 days. In comparison with the contralateral facet, neither amyloid beta plaque load nor soluble Aβ40 and Aβ42 ranges have been attenuated upon TREM2 induction.
We additional confirmed direct proof that TREM2 elevation in reactive microglia didn’t have an effect on amyloid-β pathology in plaque-bearing TgCRND8 mice by making use of anti-TREM2 neutralizing antibody to selectively block TREM2.
Our outcomes query the power of TREM2 to ameliorate established Aβ pathology, discouraging future improvement of disease-modifying pharmacological remedies concentrating on TREM2 within the late stage of AD.
 Reduced TREM2 activation in microglia of patients with Alzheimer's disease

A reporter cell system for the triggering receptor expressed on myeloid cells 2 reveals differential results of disease-associated variants on receptor signaling and activation by antibodies towards the stalk area

The triggering receptor expressed on myeloid cells 2 (TREM2) is an immune receptor expressed on myeloid-derived cell sorts. The extracellular immunoglobulin-like area of TREM2 binds anionic ligands together with Apolipoprotein E and Amyloid-β. The transmembrane area interacts with its adaptor protein DAP12/TYROBP that’s accountable for propagation of downstream signaling upon ligand interplay.
A number of sequence variants of TREM2 have been linked to completely different neurodegenerative ailments together with Alzheimer’s illness. Right here, we generated HEK 293 Flp-In cell traces stably expressing human TREM2 and DAP12 utilizing a bicistronic assemble with a T2A linker sequence permitting preliminary expression of each proteins in stoichiometric quantities.
Cell organic and biochemical analyses revealed transport of TREM2 to the cell floor, and canonical sequential proteolytic processing and shedding of TREM2 (sTREM2). The performance of this cell system was demonstrated by detection of phosphorylated spleen tyrosine kinase (SYK) upon stimulation of TREM2 with the anionic membrane lipid phosphatidylserine or anti-TREM2 antibodies.
Utilizing this cell mannequin, we demonstrated impaired signaling of illness related TREM2 variants. We additionally recognized a monoclonal antibody towards the stalk area of TREM2 with agonistic exercise. Activation of TREM2-DAP12 signaling with the monoclonal antibody and the partial lack of operate of illness related variants have been recapitulated in induced pluripotent stem cell derived microglia.
Thus, this reporter cell mannequin represents an appropriate experimental system to analyze signaling of TREM2 variants, and for the identification of ligands and compounds that modulate TREM2-DAP12 signaling.
MAIN POINTS: Illness related variants impair the signaling exercise of TREM2 by distinct mechanisms. Focusing on the stalk area of TREM2 with bivalent antibodies prompts TREM2 signaling.

Rising Microglia Biology Defines Novel Therapeutic Approaches for Alzheimer’s Illness

Alzheimer’s illness (AD) is at present untreatable, and therapeutic methods aimed to sluggish cognitive decline haven’t but been profitable. Many of those approaches have focused the amyloid cascade, indicating that novel remedy methods are required.
Latest genome-wide affiliation research (GWASs) have recognized quite a few danger elements in genes expressed in microglia, underscoring their therapeutic potential in neurodegeneration. On this assessment, we talk about how the lately outlined features of those AD danger genes will be focused therapeutically to modulate microglial cell state and sluggish the development of AD.
Antibody-mediated stimulation of the triggering receptor of myeloid cells 2 (TREM2) is on the forefront of those candidate therapeutic approaches based mostly on a mix of compelling human genetics and rising preclinical information.
This and different approaches to change microglial operate are a subject of intensive research and supply a chance for progressive AD remedies, which can be utilized alone or doubtlessly together with classical anti-amyloid therapies.

TREM2 activation on microglia promotes myelin particles clearance and remyelination in a mannequin of a number of sclerosis

A number of sclerosis (MS) is an inflammatory, demyelinating, and neurodegenerative illness of the central nervous system (CNS) triggered by autoimmune mechanisms. Microglia are essential for the clearance of myelin particles in areas of demyelination, a key step to permit remyelination.
 TREM2 is expressed by microglia and promotes microglial survival, proliferation, and phagocytic exercise. Herein we display that TREM2 was extremely expressed on myelin-laden phagocytes in energetic demyelinating lesions within the CNS of topics with MS.
In gene expression research, macrophages from topics with TREM2 genetic deficiency displayed a defect in phagocytic pathways. Remedy with a brand new TREM2 agonistic antibody promoted the clearance of myelin particles within the cuprizone mannequin of CNS demyelination.

TREM2 antibody

70R-4485 50 ug
EUR 467
Description: Rabbit polyclonal TREM2 antibody raised against the middle region of TREM2

TREM2 Antibody

1-CSB-PA024405LA01HU
  • EUR 317.00
  • EUR 335.00
  • 100ug
  • 50ug
  • Form: Liquid
  • Buffer: Preservative: 0.03% Proclin 300
    Constituents: 50% Glycerol, 0.01M PBS, pH 7.4 >95%, Protein G purified
Description: A polyclonal antibody against TREM2. Recognizes TREM2 from Human. This antibody is Unconjugated. Tested in the following application: ELISA, IHC, IF; Recommended dilution: IHC:1:20-1:200, IF:1:20-1:200

Trem2 Antibody

1-CSB-PA024405LA01MO
  • EUR 317.00
  • EUR 335.00
  • 100ug
  • 50ug
  • Form: Liquid
  • Buffer: Preservative: 0.03% Proclin 300
    Constituents: 50% Glycerol, 0.01M PBS, PH 7.4 >95%, Protein G purified
Description: A polyclonal antibody against Trem2. Recognizes Trem2 from Human, Mouse. This antibody is Unconjugated. Tested in the following application: ELISA, WB; Recommended dilution: WB:1:500-1:2000

Human Triggering Receptor Expressed On Myeloid Cells 2 (TREM2) ELISA Kit

DLR-TREM2-Hu-48T 48T
EUR 517
  • Should the Human Triggering Receptor Expressed On Myeloid Cells 2 (TREM2) ELISA Kit is proven to show malperformance, you will receive a refund or a free replacement.
Description: A sandwich quantitative ELISA assay kit for detection of Human Triggering Receptor Expressed On Myeloid Cells 2 (TREM2) in samples from serum, plasma, tissue homogenates, cell lysates or other biological fluids.

Human Triggering Receptor Expressed On Myeloid Cells 2 (TREM2) ELISA Kit

DLR-TREM2-Hu-96T 96T
EUR 673
  • Should the Human Triggering Receptor Expressed On Myeloid Cells 2 (TREM2) ELISA Kit is proven to show malperformance, you will receive a refund or a free replacement.
Description: A sandwich quantitative ELISA assay kit for detection of Human Triggering Receptor Expressed On Myeloid Cells 2 (TREM2) in samples from serum, plasma, tissue homogenates, cell lysates or other biological fluids.

Mouse Triggering Receptor Expressed On Myeloid Cells 2 (TREM2) ELISA Kit

DLR-TREM2-Mu-48T 48T
EUR 527
  • Should the Mouse Triggering Receptor Expressed On Myeloid Cells 2 (TREM2) ELISA Kit is proven to show malperformance, you will receive a refund or a free replacement.
Description: A sandwich quantitative ELISA assay kit for detection of Mouse Triggering Receptor Expressed On Myeloid Cells 2 (TREM2) in samples from serum, plasma, tissue homogenates, cell lysates or other biological fluids.

Mouse Triggering Receptor Expressed On Myeloid Cells 2 (TREM2) ELISA Kit

DLR-TREM2-Mu-96T 96T
EUR 688
  • Should the Mouse Triggering Receptor Expressed On Myeloid Cells 2 (TREM2) ELISA Kit is proven to show malperformance, you will receive a refund or a free replacement.
Description: A sandwich quantitative ELISA assay kit for detection of Mouse Triggering Receptor Expressed On Myeloid Cells 2 (TREM2) in samples from serum, plasma, tissue homogenates, cell lysates or other biological fluids.

Human Triggering Receptor Expressed On Myeloid Cells 2 (TREM2) ELISA Kit

RDR-TREM2-Hu-48Tests 48 Tests
EUR 544

Human Triggering Receptor Expressed On Myeloid Cells 2 (TREM2) ELISA Kit

RDR-TREM2-Hu-96Tests 96 Tests
EUR 756

Mouse Triggering Receptor Expressed On Myeloid Cells 2 (TREM2) ELISA Kit

RDR-TREM2-Mu-48Tests 48 Tests
EUR 557

Mouse Triggering Receptor Expressed On Myeloid Cells 2 (TREM2) ELISA Kit

RDR-TREM2-Mu-96Tests 96 Tests
EUR 774

Human Triggering Receptor Expressed On Myeloid Cells 2 (TREM2) ELISA Kit

RD-TREM2-Hu-48Tests 48 Tests
EUR 521

Human Triggering Receptor Expressed On Myeloid Cells 2 (TREM2) ELISA Kit

RD-TREM2-Hu-96Tests 96 Tests
EUR 723

Mouse Triggering Receptor Expressed On Myeloid Cells 2 (TREM2) ELISA Kit

RD-TREM2-Mu-48Tests 48 Tests
EUR 533

Mouse Triggering Receptor Expressed On Myeloid Cells 2 (TREM2) ELISA Kit

RD-TREM2-Mu-96Tests 96 Tests
EUR 740

TREM2 Conjugated Antibody

C40390 100ul
EUR 397

Trem2 Polyclonal Antibody

A61478 100 µg
EUR 570.55
Description: reagents widely cited

TREM2 Polyclonal Antibody

ABP60750-003ml 0.03ml
EUR 158
  • Immunogen information: Synthesized peptide derived from part region of human TREM2 protein
  • Applications tips:
Description: A polyclonal antibody for detection of TREM2 from Human, Mouse. This TREM2 antibody is for WB, ELISA. It is affinity-purified from rabbit serum by affinity-chromatography using the specific immunogenand is unconjugated. The antibody is produced in rabbit by using as an immunogen synthesized peptide derived from part region of human TREM2 protein

TREM2 Polyclonal Antibody

ABP60750-01ml 0.1ml
EUR 289
  • Immunogen information: Synthesized peptide derived from part region of human TREM2 protein
  • Applications tips:
Description: A polyclonal antibody for detection of TREM2 from Human, Mouse. This TREM2 antibody is for WB, ELISA. It is affinity-purified from rabbit serum by affinity-chromatography using the specific immunogenand is unconjugated. The antibody is produced in rabbit by using as an immunogen synthesized peptide derived from part region of human TREM2 protein

TREM2 Polyclonal Antibody

ABP60750-02ml 0.2ml
EUR 414
  • Immunogen information: Synthesized peptide derived from part region of human TREM2 protein
  • Applications tips:
Description: A polyclonal antibody for detection of TREM2 from Human, Mouse. This TREM2 antibody is for WB, ELISA. It is affinity-purified from rabbit serum by affinity-chromatography using the specific immunogenand is unconjugated. The antibody is produced in rabbit by using as an immunogen synthesized peptide derived from part region of human TREM2 protein

TREM2 Polyclonal Antibody

ES11070-100ul 100ul
EUR 279
Description: A Rabbit Polyclonal antibody against TREM2 from Human/Mouse. This antibody is tested and validated for WB, ELISA, WB, ELISA

TREM2 Polyclonal Antibody

ES11070-50ul 50ul
EUR 207
Description: A Rabbit Polyclonal antibody against TREM2 from Human/Mouse. This antibody is tested and validated for WB, ELISA, WB, ELISA

Anti-TREM2 antibody

STJ112507 100 µl
EUR 277
Description: This gene encodes a membrane protein that forms a receptor signaling complex with the TYRO protein tyrosine kinase binding protein. The encoded protein functions in immune response and may be involved in chronic inflammation by triggering the production of constitutive inflammatory cytokines. Defects in this gene are a cause of polycystic lipomembranous osteodysplasia with sclerosing leukoencephalopathy (PLOSL). Alternative splicing results in multiple transcript variants encoding different isoforms.

Anti-TREM2 antibody

STJ71241 100 µg
EUR 359

Anti-TREM2 antibody

STJ192228 200 µl
EUR 197
Description: Unconjugated Rabbit polyclonal to TREM2

TREM2 siRNA

20-abx937978
  • EUR 551.00
  • EUR 732.00
  • 15 nmol
  • 30 nmol
  • Shipped within 5-10 working days.

TREM2 siRNA

20-abx937979
  • EUR 551.00
  • EUR 732.00
  • 15 nmol
  • 30 nmol
  • Shipped within 5-10 working days.

TREM2 Antibody, HRP conjugated

1-CSB-PA024405LB01HU
  • EUR 317.00
  • EUR 335.00
  • 100ug
  • 50ug
  • Form: Liquid
  • Buffer: Preservative: 0.03% Proclin 300
    Constituents: 50% Glycerol, 0.01M PBS, pH 7.4 >95%, Protein G purified
Description: A polyclonal antibody against TREM2. Recognizes TREM2 from Human. This antibody is HRP conjugated. Tested in the following application: ELISA

Trem2 Antibody, HRP conjugated

1-CSB-PA024405LB01MO
  • EUR 317.00
  • EUR 335.00
  • 100ug
  • 50ug
  • Form: Liquid
  • Buffer: Preservative: 0.03% Proclin 300
    Constituents: 50% Glycerol, 0.01M PBS, PH 7.4 >95%, Protein G purified
Description: A polyclonal antibody against Trem2. Recognizes Trem2 from Mouse. This antibody is HRP conjugated. Tested in the following application: ELISA

TREM2 Antibody, FITC conjugated

1-CSB-PA024405LC01HU
  • EUR 317.00
  • EUR 335.00
  • 100ug
  • 50ug
  • Form: Liquid
  • Buffer: Preservative: 0.03% Proclin 300
    Constituents: 50% Glycerol, 0.01M PBS, pH 7.4 >95%, Protein G purified
Description: A polyclonal antibody against TREM2. Recognizes TREM2 from Human. This antibody is FITC conjugated. Tested in the following application: ELISA

Trem2 Antibody, FITC conjugated

1-CSB-PA024405LC01MO
  • EUR 317.00
  • EUR 335.00
  • 100ug
  • 50ug
  • Form: Liquid
  • Buffer: Preservative: 0.03% Proclin 300
    Constituents: 50% Glycerol, 0.01M PBS, PH 7.4 >95%, Protein G purified
Description: A polyclonal antibody against Trem2. Recognizes Trem2 from Mouse. This antibody is FITC conjugated. Tested in the following application: ELISA

TREM2 Antibody, Biotin conjugated

1-CSB-PA024405LD01HU
  • EUR 317.00
  • EUR 335.00
  • 100ug
  • 50ug
  • Form: Liquid
  • Buffer: Preservative: 0.03% Proclin 300
    Constituents: 50% Glycerol, 0.01M PBS, pH 7.4 >95%, Protein G purified
Description: A polyclonal antibody against TREM2. Recognizes TREM2 from Human. This antibody is Biotin conjugated. Tested in the following application: ELISA

Trem2 Antibody, Biotin conjugated

1-CSB-PA024405LD01MO
  • EUR 317.00
  • EUR 335.00
  • 100ug
  • 50ug
  • Form: Liquid
  • Buffer: Preservative: 0.03% Proclin 300
    Constituents: 50% Glycerol, 0.01M PBS, PH 7.4 >95%, Protein G purified
Description: A polyclonal antibody against Trem2. Recognizes Trem2 from Mouse. This antibody is Biotin conjugated. Tested in the following application: ELISA

Anti-Trem2 (mouse) antibody

STJ71242 100 µg
EUR 359

TREM2 Rabbit pAb

A10482-100ul 100 ul
EUR 308

TREM2 Rabbit pAb

A10482-200ul 200 ul
EUR 459

TREM2 Rabbit pAb

A10482-20ul 20 ul
EUR 183
Results included enhancement of myelin uptake and degradation, leading to accelerated myelin particles elimination by microglia. Most significantly, antibody-dependent TREM2 activation on microglia elevated density of oligodendrocyte precursors in areas of demyelination, in addition to the formation of mature oligodendrocytes thus enhancing remyelination and axonal integrity.
These outcomes are related as they suggest TREM2 on microglia as a possible new goal to advertise remyelination.

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