Journal: Acta Neuropathologica Communications

Article Title: Spatial characterisation of TREM2 expression in actively demyelinating multiple sclerosis lesions supports its key roles in lipid metabolic pathways

doi: 10.1186/s40478-026-02241-x

Figure Lengend Snippet: Spatial transcriptomics in hippocampal tissue containing chronic active lesions from two cases (MS13C and MS15A) of secondary progressive MS. a Schematic of spatial transcriptomics workflow using sample integration, clustering and deconvolution functions. b LFB staining and MHC class II immunohistochemistry were used to identify lesioned (yellow outline) areas (2 mm scale bar; left panels). c Cell populations were estimated by deconvolution analysis of spatial gene expression profiles in each cluster. Clusters 0, 4, 11, 14, 15, and 16 contained a higher proportion of glial cells relative to other clusters associated with neuronal cell types in the hippocampus. d Quantitative analysis of spatial distributions of total TREM2 + spots and TREM2 in relation to selected myeloid cell markers ( CD68, CD163, IBA1 ). OPC = Oligodendrocyte progenitor cell, vSMC = Vascular smooth muscle cell, OLG = Oligodendrocyte

Article Snippet: Rabbit anti-human TREM2 (Polyclonal) , Nonspecific , Cusabio, US (CSB-PA024405LA01HU) , 1:100.

Techniques: Spatial Transcriptomics, Staining, Immunohistochemistry, Gene Expression

Journal: Acta Neuropathologica Communications

Article Title: Spatial characterisation of TREM2 expression in actively demyelinating multiple sclerosis lesions supports its key roles in lipid metabolic pathways

doi: 10.1186/s40478-026-02241-x

Figure Lengend Snippet: Gene enrichment pathway analysis of module B revealed lesion-associated submodules, with TREM2 enriched exclusively in submodule B. a Submodules of original module B for the two cases MS13C and MS15A allowed the identification of submodules associated with distinct glial cell states. b Heat map of the cellular composition of each submodule for MS13C and MS15A. c Submodule B hub gene network for MS13C revealed TREM2 and proximal genes. d Gene ontology biological process enrichment analysis for each submodule for MS15A and MS13C. e The results of enrichment analysis within the KEGG gene sets database for co-expressed glial submodules for MS13C and MS15A are shown. OPC = Oligodendrocyte progenitor cell, vSMC = Vascular smooth muscle cell, OLG = Oligodendrocyte, GO = Gene ontology

Article Snippet: Rabbit anti-human TREM2 (Polyclonal) , Nonspecific , Cusabio, US (CSB-PA024405LA01HU) , 1:100.

Techniques:

Journal: Acta Neuropathologica Communications

Article Title: Spatial characterisation of TREM2 expression in actively demyelinating multiple sclerosis lesions supports its key roles in lipid metabolic pathways

doi: 10.1186/s40478-026-02241-x

Figure Lengend Snippet: Heat map highlighting heterogeneity of TREM2 protein expression in myeloid cells in MS lesions, MS and control NAWM. NAWM and lesion sub-areas were analysed (lesion centres, PLWM and lesion rims). Staining intensity for ORO, CD68+, MHC class II+ and, MBP+ for each tissue are shown. ORO+ cells per ROI (314.74 × 236.06 microns) ranged from 0 to 30 + cells. CD68+ or MHC class II+ cells per ROI (500 × 500 microns) ranged from 0 to 100+ cells. Relative MBP immunohistochemistry was characterised as “light”, “med” and “dark”. The three main cell types analysed were: PVMs (left), parenchymal macrophages (middle) and microglia (right). Images used to calculate the average number of immunolabeled cells per ROI were 312.39 × 312.39 µm. *Tissue lesions provided by Washington University Repository were identified by LFB and MHC class II staining. **MS3E was a case with active MS lesions, which subsequently was identified to have progressive multifocal leukoencephalopathy. This case was not included in subsequent overall analyses of the cohort of MS lesion cases. ***MS15A was a chronic active lesion confirmed by a neuropathologist, however the section provided did not have a clearly identifiable rim. ORO = Oil Red O, MBP = Myelin Basic Protein, NAWM = Normal-appearing white matter, PLWM = Perilesional white matter, n.a = not applicable, ROI = Region of Interest, MHC = MHC class II

Article Snippet: Rabbit anti-human TREM2 (Polyclonal) , Nonspecific , Cusabio, US (CSB-PA024405LA01HU) , 1:100.

Techniques: Expressing, Control, Staining, Immunohistochemistry, Immunolabeling

Journal: Acta Neuropathologica Communications

Article Title: Spatial characterisation of TREM2 expression in actively demyelinating multiple sclerosis lesions supports its key roles in lipid metabolic pathways

doi: 10.1186/s40478-026-02241-x

Figure Lengend Snippet: Characterisation of TREM2 expression on microglia and macrophages in active lesions. a Representative Luxol Fast Blue (LFB) and Oil Red O (ORO) images from MS2A highlight the histopathology of an active MS lesion. Lipid-filled cells in the active lesion are highlighted by LFB staining (left; 25 µm scale bar) and ORO staining (middle; yellow dotted box highlights the area of the right image; 10 µm scale bar). Arrows point to LFB staining inside PVMs (possibly indicative of intracellular myelin products—white arrow), ORO + cells in the CNS parenchyma (white star) and lining the vessel (white arrow) (×40 magnification). b Representative immunofluorescence images of macrophages (left), reactive microglia (centre), and PVMs (right) are from active lesions (from MS2A and MS4A) (×40 magnification; 30 µm scale bar). Cropped images are from the highlighted area in the merged overview (yellow square). The area has been split into separate channels: TREM2 (red), CD163 (green) and Iba1 (white). DAPI-stained nuclei (blue) are only seen in the merged overview images. The white arrow marks a triple-labelled TREM2+ CD163+ Iba1+ macrophage. The star marks a rare putative triple-labelled TREM2+ CD163+ Iba1+ microglia. In this panel, other reactive microglia can be seen that are negative for CD163. c TREM2 (red), CD163 (green) and Iba1 (white) triple-labelled macrophages in the choroid plexus (white arrow) from MS15A (20 µm scale bar)

Article Snippet: Rabbit anti-human TREM2 (Polyclonal) , Nonspecific , Cusabio, US (CSB-PA024405LA01HU) , 1:100.

Techniques: Expressing, Histopathology, Staining, Immunofluorescence

Journal: Acta Neuropathologica Communications

Article Title: Spatial characterisation of TREM2 expression in actively demyelinating multiple sclerosis lesions supports its key roles in lipid metabolic pathways

doi: 10.1186/s40478-026-02241-x

Figure Lengend Snippet: Perinuclear and plasma membrane distribution of TREM2 respectively in microglia and macrophages in MS lesions. Actively demyelinating tissues were immunolabelled with TREM2 (red), CD163 (green), Iba1 (white), counter-stained with DAPI (blue; merged images), and imaged using a 100× objective with 6-step confocal z-stacks. a Triple labelled PVM–CD163+ TREM2+ Iba1+ (case MS4A). Punctuate discontinuous labelling with the AF1828 antibody in a thin line around the inner surface of the vessel can also be seen, indicative of endothelium (arrow). b TREM2+ CD163-negative microglia (MS2A), c TREM2+ CD163+ putative microglia (MS2A), d TREM2-negative CD163+ putative microglia (MS4A), e CD163+ TREM2+ macrophage (MS2A). f A rare TREM2+ CD163-negative Iba1-negative cell (white arrow) (MS4A). Scale bars = 5 µm

Article Snippet: Rabbit anti-human TREM2 (Polyclonal) , Nonspecific , Cusabio, US (CSB-PA024405LA01HU) , 1:100.

Techniques: Clinical Proteomics, Membrane, Staining

Journal: Acta Neuropathologica Communications

Article Title: Spatial characterisation of TREM2 expression in actively demyelinating multiple sclerosis lesions supports its key roles in lipid metabolic pathways

doi: 10.1186/s40478-026-02241-x

Figure Lengend Snippet: Quantification of TREM2+ cells in control NAWM, MS NAWM and MS lesions. a Number of cells (total DAPI nuclei) per mm 2 , b number of microglia/macrophages (Iba1+ and/or CD163+) per mm 2 , c number of TREM2+ microglia/macrophages per mm 2 , and d percentage of TREM2+ microglia/macrophages in distinct tissue areas as indicated. e Proportions of single, double, and triple labelled TREM2+ CD163+ Iba1+ cell populations in distinct tissue areas. The four most abundant cell phenotypes for each area are listed below each chart. Each cell phenotype has been referenced with the same colour across different lesion types as indicate in figure legend. f Immunofluorescence intensity of TREM2 (pink), Iba1 (blue) and CD163 (green) in distinct tissue areas. The size of the individual cell region of interest used to determine intensity ranged from 64 to 295 µm 2 . * P ≤ 0.05; ** P ≤ 0.01; **** P ≤ 0.0001. NAWM = normal-appearing white matter (from MS cases or controls as indicated), LC = lesion centre, PLWM = perilesional white matter, LR = lesion rim

Article Snippet: Rabbit anti-human TREM2 (Polyclonal) , Nonspecific , Cusabio, US (CSB-PA024405LA01HU) , 1:100.

Techniques: Control, Immunofluorescence

Journal: Acta Neuropathologica Communications

Article Title: Spatial characterisation of TREM2 expression in actively demyelinating multiple sclerosis lesions supports its key roles in lipid metabolic pathways

doi: 10.1186/s40478-026-02241-x

Figure Lengend Snippet: TREM2 co-expression with lipid metabolism and activation markers. a TREM2 (red), MHC class II (green), and PLIN2 (white) immunolabelling in parenchymal macrophages (top) and perivascular macrophages (bottom) from an active lesion centre (MS2A). b Quantification per mm 2 of number of PLIN2+ cells, PLIN2+ TREM2+ cells and the proportion of all PLIN2+ cells that are TREM2+ in different tissue areas. All TREM2+ cells were PLIN2+. c TREM2 (red), CD68 (green) and TMEM119 (white) indicate TREM2 expression in active microglia in the lesion centre (top) and PLWM (bottom). DAPI nuclei counterstain is shown in the merged channels (100× objective; 10 µm scale bar) (MS4A). NAWM = Normal-appearing white matter, LC = lesion centre, PLWM = Perilesional white matter, LR = lesion rim

Article Snippet: Rabbit anti-human TREM2 (Polyclonal) , Nonspecific , Cusabio, US (CSB-PA024405LA01HU) , 1:100.

Techniques: Expressing, Activation Assay

Journal: Acta Neuropathologica Communications

Article Title: Spatial characterisation of TREM2 expression in actively demyelinating multiple sclerosis lesions supports its key roles in lipid metabolic pathways

doi: 10.1186/s40478-026-02241-x

Figure Lengend Snippet: TREM2 and MS4A4A expression in a PML and active MS lesion. a ORO staining of a PML lesion (20× objective; 200 µm scale bar). The insert (left) shows lipid-filled round macrophage infiltrates characteristic of PML (40× objective; 20 µm scale bar). b TREM2 (red), CD163 (green) and Iba1 (white) immunofluorescence with DAPI nuclei counterstain (blue), highlights abundant CD163+ TREM2+ Iba1+ triple labelled macrophages in the PML lesion with TREM2 distributed to the plasma membrane of foamy macrophages (merge panel 30 µm scale bar; right panels 5 µm scale bar). c TREM2 (red), TMEM119 (white), CD163 (green) and DAPI (blue), 20 µm scale bar. d TREM2 (red), MS4A4A (white) and DAPI (blue), 20 µm scale bar. e TREM2 (red), TMEM119 (white), CD163 (green) and DAPI (blue; merged image) indicate TREM2+ microglia in peri-lesional white matter in PML (10 µm scale bar). f TREM2 (red), CD68 (green) and MS4A4A (white) indicate TREM2 and MS4A4A co-expression in PVMs from an active MS lesion centre (MS4A). DAPI nuclei counterstain is shown in the merged channels (100× objective; 10 µm scale bar). Representative images in a–e are of tissue from PML case MS3E. PLWM = Perilesional white matter, PML = Progressive multifocal leukoencephalopathy

Article Snippet: Rabbit anti-human TREM2 (Polyclonal) , Nonspecific , Cusabio, US (CSB-PA024405LA01HU) , 1:100.

Techniques: Expressing, Staining, Immunofluorescence, Clinical Proteomics, Membrane

Journal: Frontiers in Cellular Neuroscience

Article Title: TREM2 Regulates Heat Acclimation-Induced Microglial M2 Polarization Involving the PI3K-Akt Pathway Following EMF Exposure

doi: 10.3389/fncel.2019.00591

Figure Lengend Snippet: Effects of HA on the expression of triggering receptor expressed on myeloid cells-2 (TREM2) and the phosphorylation of PI3K and Akt in EMF-stimulated N9 cells. N9 cells were pretreated with or without a 72-h HA process (20/4-h cycle of 37°C/39.5°C) and then exposed to 2.45-GHz EMF or sham-exposed for 20 min. Levels of TREM2 (A) , and phosphorylation of PI3K and Akt (B) in total cell lysates were analyzed using Western blotting, and the corresponding densitometric analyses were represented. Data are presented as means ± SEM of three independent experiments. * P < 0.05 vs. the sham-exposed control group; # P < 0.05 vs. the EMF-exposed group.

Article Snippet: The cells were incubated with rat anti-mouse TREM2 (Merck Millipore), rabbit anti-mouse phosphor-Ser473-Akt (Cell Signaling Technology, Danvers, MA, USA), and/or mouse anti-mouse CD206 (Santa Cruz) antibodies at 37°C for 1 h. After being washed, the slides were incubated for 1 h at 37 °C with rabbit anti-mouse AlexaFluor 488 (Life Technologies, Carlsbad, CA, USA), goat anti-rat CF568 (Sigma–Aldrich, St. Louis, MO, USA), and chicken anti-rabbit CF633 antibodies (Sigma–Aldrich, St. Louis, MO, USA) in the dark.

Techniques: Expressing, Phospho-proteomics, Western Blot, Control

Journal: Frontiers in Cellular Neuroscience

Article Title: TREM2 Regulates Heat Acclimation-Induced Microglial M2 Polarization Involving the PI3K-Akt Pathway Following EMF Exposure

doi: 10.3389/fncel.2019.00591

Figure Lengend Snippet: Effects of TREM2 esiRNA on M2 microglial phenotype regulation in EMF-stimulated N9 cells with HA preconditioning. N9 cells were transfected with or without TREM2 esiRNA (20 nM) at 60 h during the uncompleted 72-h HA and then continuously cultured 12 h to complete the HA process and the 24 h transfection of TREM2 esiRNA. Western blotting quantification of TREM2 (A) , and M2 markers CD206 and Arg1 (C) , and ELISA of anti-inflammatory cytokines IL-4 and IL-10 (B) production of in either control or HA-plus-EMF-treated N9 cells with or without TREM2 esiRNA. Data are presented as means ± SEM of three independent experiments. * P < 0.05 vs. the non-HA and sham-exposed control group; # P < 0.05 vs. the HA-plus-EMF-exposed group. (D) Confocal immunofluorescence microscopy was performed on cultures that were immunoreacted with antibodies against TREM2 and CD206 with esi-TREM2 treatment in HA-plus-EMF-treated N9 cells. Scale bar: 20 μm.

Article Snippet: The cells were incubated with rat anti-mouse TREM2 (Merck Millipore), rabbit anti-mouse phosphor-Ser473-Akt (Cell Signaling Technology, Danvers, MA, USA), and/or mouse anti-mouse CD206 (Santa Cruz) antibodies at 37°C for 1 h. After being washed, the slides were incubated for 1 h at 37 °C with rabbit anti-mouse AlexaFluor 488 (Life Technologies, Carlsbad, CA, USA), goat anti-rat CF568 (Sigma–Aldrich, St. Louis, MO, USA), and chicken anti-rabbit CF633 antibodies (Sigma–Aldrich, St. Louis, MO, USA) in the dark.

Techniques: esiRNA, Transfection, Cell Culture, Western Blot, Enzyme-linked Immunosorbent Assay, Control, Immunofluorescence, Microscopy

Journal: Frontiers in Cellular Neuroscience

Article Title: TREM2 Regulates Heat Acclimation-Induced Microglial M2 Polarization Involving the PI3K-Akt Pathway Following EMF Exposure

doi: 10.3389/fncel.2019.00591

Figure Lengend Snippet: Effects of TREM2 esiRNA and the PI3K inhibitor LY294002 on the phosphorylation of PI3K and Akt in EMF-stimulated N9 cells with HA preconditioning. N9 cells were transfected with or without TREM2 esiRNA (20 nM) at 60 h during the uncompleted 72-h HA and then continuously cultured 12 h to complete the HA process and the 24 h transfection of TREM2 esiRNA. Alternatively, N9 cells were treated with or without LY294002 (10 μM) for 30 min prior to the end of the 72-h HA process. Levels of PI3K and Akt phosphorylation in total cell lysates were analyzed using Western blotting, and the corresponding densitometric analyses were represented. Data are presented as means ± SEM of three independent experiments. * P < 0.05 vs. the non-HA and sham-exposed control group; # P < 0.05 vs. the HA-plus-EMF-exposed group.

Article Snippet: The cells were incubated with rat anti-mouse TREM2 (Merck Millipore), rabbit anti-mouse phosphor-Ser473-Akt (Cell Signaling Technology, Danvers, MA, USA), and/or mouse anti-mouse CD206 (Santa Cruz) antibodies at 37°C for 1 h. After being washed, the slides were incubated for 1 h at 37 °C with rabbit anti-mouse AlexaFluor 488 (Life Technologies, Carlsbad, CA, USA), goat anti-rat CF568 (Sigma–Aldrich, St. Louis, MO, USA), and chicken anti-rabbit CF633 antibodies (Sigma–Aldrich, St. Louis, MO, USA) in the dark.

Techniques: esiRNA, Phospho-proteomics, Transfection, Cell Culture, Western Blot, Control

Journal: Alzheimer's & Dementia : Translational Research & Clinical Interventions

Article Title: Alzheimer's disease drug development pipeline: 2021

doi: 10.1002/trc2.12179

Figure Lengend Snippet: Agents in Phase 2 of Alzheimer's disease drug development (ClinicalTrials.gov accessed January 5, 2021)

Article Snippet: AL002 , Inflammation , Monoclonal antibody targeting TREM2 receptors to promote microglial clearance of Aβ , DMT , Recruiting (NCT04592874) , Alector, AbbVie , Nov 2020 , Aug 2023.

Techniques: Infection, Activity Assay, Binding Assay, Expressing, Reverse Transcription, Phospho-proteomics