Journal: bioRxiv

Article Title: Phage Display-Derived Cyclic Peptides Target TREM2 and Modulate Microglial Responses under Amyloid Stress

doi: 10.64898/2026.04.22.720287

Figure Lengend Snippet: (A) Schematic of the phage display workflow. The extracellular domain of TREM2 was used as the target for selection from a cysteine-constrained cyclic peptide M13 phage library. Four rounds of biopanning, including binding, washing, elution, and amplification, were performed to enrich TREM2-binding clones. (B) Top enriched peptide sequences identified from rounds 2-4. Filled circles indicate detection of a given sequence in the corresponding round, while open circles indicate absence. All sequences conform to a cysteine-constrained cyclic peptide scaffold. (C) Phage ELISA validation of selected peptides. Binding signals are presented as the ratio of signal obtained in TREM2-coated wells relative to control wells lacking protein (E/C). Values above 1 indicate preferential binding to TREM2. Data are shown as mean ± SEM (n=3).

Article Snippet: A 10 μM solution of the His-tagged TREM2 ectodomain (SinoBiological, 11084-H08H) was labeled using the RED-maleimide 2 nd generation dye (NanoTemper, MO-L014) according to the manufacturer’s protocol (labeling buffer: 10 mM HEPES pH 7.4, 150 mM NaCl, 0.5 mM TCEP, 0.05% Tween-20), resulting in a 0.90 μM stock of labeled protein (“TREM2-maleimide-dye”) in storage buffer (HBSP: 10 mM HEPES pH 7.4, 150 mM NaCl, 0.05% Tween-20) with a final degree of labeling (DOL) of 0.596.

Techniques: Selection, Binding Assay, Amplification, Clone Assay, Sequencing, Enzyme-linked Immunosorbent Assay, Biomarker Discovery, Control

Journal: bioRxiv

Article Title: Phage Display-Derived Cyclic Peptides Target TREM2 and Modulate Microglial Responses under Amyloid Stress

doi: 10.64898/2026.04.22.720287

Figure Lengend Snippet:

Article Snippet: A 10 μM solution of the His-tagged TREM2 ectodomain (SinoBiological, 11084-H08H) was labeled using the RED-maleimide 2 nd generation dye (NanoTemper, MO-L014) according to the manufacturer’s protocol (labeling buffer: 10 mM HEPES pH 7.4, 150 mM NaCl, 0.5 mM TCEP, 0.05% Tween-20), resulting in a 0.90 μM stock of labeled protein (“TREM2-maleimide-dye”) in storage buffer (HBSP: 10 mM HEPES pH 7.4, 150 mM NaCl, 0.05% Tween-20) with a final degree of labeling (DOL) of 0.596.

Techniques: Binding Assay

Journal: bioRxiv

Article Title: Phage Display-Derived Cyclic Peptides Target TREM2 and Modulate Microglial Responses under Amyloid Stress

doi: 10.64898/2026.04.22.720287

Figure Lengend Snippet: (A) IL-1β secretion in human iPSC-derived microglia following Aβ 1-42 oligomer challenge in the presence of TREM2-6 or TREM2-12 (5, 10, and 25 µM). VG-3927 (5 μM) was used as a positive control. Data are normalized to the Aβ-treated vehicle control and expressed as percent change. (B) Loss of peptide-mediated suppression of IL-1β secretion in TREM2 knockout (KO) microglia confirms TREM2-dependent activity. (C) Modulation of secreted ApoE levels in human microglia following Aβ exposure and peptide treatment (25 µM). ApoE levels are normalized to vehicle-treated controls. Data are presented as mean ± SD (n = 5). Statistical significance was determined by one-way or two-way ANOVA with Dunnett’s post hoc test. ns , not significant; p < 0.05 (*), p < 0.01 (**), p < 0.001 (***), and p < 0.0001 (****) relative to vehicle treatment.

Article Snippet: A 10 μM solution of the His-tagged TREM2 ectodomain (SinoBiological, 11084-H08H) was labeled using the RED-maleimide 2 nd generation dye (NanoTemper, MO-L014) according to the manufacturer’s protocol (labeling buffer: 10 mM HEPES pH 7.4, 150 mM NaCl, 0.5 mM TCEP, 0.05% Tween-20), resulting in a 0.90 μM stock of labeled protein (“TREM2-maleimide-dye”) in storage buffer (HBSP: 10 mM HEPES pH 7.4, 150 mM NaCl, 0.05% Tween-20) with a final degree of labeling (DOL) of 0.596.

Techniques: Derivative Assay, Positive Control, Control, Knock-Out, Activity Assay

Journal: bioRxiv

Article Title: Phage Display-Derived Cyclic Peptides Target TREM2 and Modulate Microglial Responses under Amyloid Stress

doi: 10.64898/2026.04.22.720287

Figure Lengend Snippet: Quantification of PSD95 levels in human iPSC-derived neuron-microglia co-cultures following Aβ 1-42 oligomer exposure and treatment with TREM2-6 or TREM2-12 (5, 10, and 25 µM). VG-3927 (5 μM) was used as a positive control. PSD95 levels are expressed as percent rescue relative to Aβ-treated vehicle controls. Data are presented as mean ± SD (n = 5). Statistical significance was assessed by one-way ANOVA with Dunnett’s post hoc test. p < 0.05 (*), p < 0.01 (**), p < 0.001 (***), and p < 0.0001 (****) relative to vehicle treatment.

Article Snippet: A 10 μM solution of the His-tagged TREM2 ectodomain (SinoBiological, 11084-H08H) was labeled using the RED-maleimide 2 nd generation dye (NanoTemper, MO-L014) according to the manufacturer’s protocol (labeling buffer: 10 mM HEPES pH 7.4, 150 mM NaCl, 0.5 mM TCEP, 0.05% Tween-20), resulting in a 0.90 μM stock of labeled protein (“TREM2-maleimide-dye”) in storage buffer (HBSP: 10 mM HEPES pH 7.4, 150 mM NaCl, 0.05% Tween-20) with a final degree of labeling (DOL) of 0.596.

Techniques: Derivative Assay, Positive Control

Journal: bioRxiv

Article Title: Phage Display-Derived Cyclic Peptides Target TREM2 and Modulate Microglial Responses under Amyloid Stress

doi: 10.64898/2026.04.22.720287

Figure Lengend Snippet: (A) Time-dependent root-mean-square deviation (RMSD) of the TREM2 receptor in the free form (cyan line) and in complex with T6 (purple line) and T12 (yellow line) over a 100 ns MD simulation. (B) RMSD of the T6 and T12 over a 100-ns MD simulation.

Article Snippet: A 10 μM solution of the His-tagged TREM2 ectodomain (SinoBiological, 11084-H08H) was labeled using the RED-maleimide 2 nd generation dye (NanoTemper, MO-L014) according to the manufacturer’s protocol (labeling buffer: 10 mM HEPES pH 7.4, 150 mM NaCl, 0.5 mM TCEP, 0.05% Tween-20), resulting in a 0.90 μM stock of labeled protein (“TREM2-maleimide-dye”) in storage buffer (HBSP: 10 mM HEPES pH 7.4, 150 mM NaCl, 0.05% Tween-20) with a final degree of labeling (DOL) of 0.596.

Techniques:

Journal: bioRxiv

Article Title: Phage Display-Derived Cyclic Peptides Target TREM2 and Modulate Microglial Responses under Amyloid Stress

doi: 10.64898/2026.04.22.720287

Figure Lengend Snippet: B) Structural snapshot clustered from the late stage of the MD simulation of T12 (A) and T6 (B) complexed with TREM2. The receptor is shown in grey cartoon, T12 is shown in blue sticks, and T6 is shown in orange sticks. (C and D) Views of the binding interface between T12 (C) / T6 (D) and TREM2 with the key interacting residues on both sides and yellow dashed lines that demonstrate stable hydrogen bonds and salt bridges.

Article Snippet: A 10 μM solution of the His-tagged TREM2 ectodomain (SinoBiological, 11084-H08H) was labeled using the RED-maleimide 2 nd generation dye (NanoTemper, MO-L014) according to the manufacturer’s protocol (labeling buffer: 10 mM HEPES pH 7.4, 150 mM NaCl, 0.5 mM TCEP, 0.05% Tween-20), resulting in a 0.90 μM stock of labeled protein (“TREM2-maleimide-dye”) in storage buffer (HBSP: 10 mM HEPES pH 7.4, 150 mM NaCl, 0.05% Tween-20) with a final degree of labeling (DOL) of 0.596.

Techniques: Binding Assay

Journal: Brain, Behavior, & Immunity - Health

Article Title: Increased circulating TREM2 + microglial extracellular vesicles in aged APP/PS1 Alzheimer's disease rats

doi: 10.1016/j.bbih.2026.101261

Figure Lengend Snippet: TMEM119 + /TREM2 + EVs are increased in 15-month-old APP/PS1 rats. A) Example nanoscale flow cytometry scatter plots of TMEM119, TREM2 and dual-positive EVs. B) TMEM119 + /TREM2 + events/μl labelled in 3-, 9-, and 15-month wildtype and APP/PS1 rat plasma assessed using a 2-way ANOVA (genotype ✕ sex). C) Size distribution of TMEM119 +/ TREM2 + EVs based on standardized reference beads. D) Western blot of TMEM119 and TREM2 from, immunoprecipitated TMEM119 EVs, total rat plasma EVs, and whole cell lysate. E) Representative immunofluorescent 20 ✕ images of TMEM119 and TREM2 in 15-month-old APP/PS1 hippocampus. Scale bar indicates 10 μm ∗ Indicates statistical significance ( p < 0.05) Data represent the group mean ± SEM. n = 10-12 males and females per group. LALS, long angle light scatter; SALS, short angle light scatter.

Article Snippet: Membranes were washed for 3 × 10 min with TBST prior to incubation with anti-mouse (TMEM119, ⍺-tubulin) or anti-rabbit (TREM2) HRP-conjugated secondary antibodies (1:10,000, Jackson Laboratories) for 1 h at room temperature.

Techniques: Flow Cytometry, Clinical Proteomics, Western Blot, Immunoprecipitation

Journal: Brain, Behavior, & Immunity - Health

Article Title: Increased circulating TREM2 + microglial extracellular vesicles in aged APP/PS1 Alzheimer's disease rats

doi: 10.1016/j.bbih.2026.101261

Figure Lengend Snippet: TREM2 mRNA and protein levels differ by age and genotype in the hippocampus. A) Coronal section for the hippocampal region of interest. B) qPCR measurement of TMEM119 and TREM2 in 3-, 9-, and 15-month WT and APP/PS1 hippocampal RNA isolates assessed using 2-way ANOVAs (age ✕ genotype). C-E) Western blot of TMEM119 and TREM2 and corresponding quantification in hippocampal protein isolates from 3-, 9-, and 15-month WT and APP/PS1 rats assessed using t -tests. ∗ Indicates statistical significance ( p < 0.05). Data represent the group mean ± SEM. n = 2-3 males and 2-3 females per group.

Article Snippet: Membranes were washed for 3 × 10 min with TBST prior to incubation with anti-mouse (TMEM119, ⍺-tubulin) or anti-rabbit (TREM2) HRP-conjugated secondary antibodies (1:10,000, Jackson Laboratories) for 1 h at room temperature.

Techniques: Western Blot

Journal: Brain, Behavior, & Immunity - Health

Article Title: Increased circulating TREM2 + microglial extracellular vesicles in aged APP/PS1 Alzheimer's disease rats

doi: 10.1016/j.bbih.2026.101261

Figure Lengend Snippet: Increased TREM2 mRNA in the corpus callosum of 15-month-old rats. A) Coronal section for the corpus callosum region of interest. B) qPCR measurement of TMEM119 and TREM2 in 3-, 9-, and 15-month WT and APP/PS1 corpus callosum RNA isolates assessed using 2-way ANOVAs (age ✕ genotype). C-E) Western blot of TMEM119 and TREM2 and corresponding quantification in corpus callosum protein isolates from 3-, 9-, and 15-month WT and APP/PS1 rats assessed using t -tests. ∗ Indicates statistical significance ( p < 0.05). Data represent the group mean ± SEM. n = 2-3 males and 2-3 females per group.

Article Snippet: Membranes were washed for 3 × 10 min with TBST prior to incubation with anti-mouse (TMEM119, ⍺-tubulin) or anti-rabbit (TREM2) HRP-conjugated secondary antibodies (1:10,000, Jackson Laboratories) for 1 h at room temperature.

Techniques: Western Blot

Journal: Brain, Behavior, & Immunity - Health

Article Title: Increased circulating TREM2 + microglial extracellular vesicles in aged APP/PS1 Alzheimer's disease rats

doi: 10.1016/j.bbih.2026.101261

Figure Lengend Snippet: Increased histological TREM2 expression in aged APP/PS1 rats. A) Quantification of TREM2 cell density in the hippocampus of 3-, 9-, and 15-month WT and APP/PS1 rats assessed using t -tests. B) Representative 20 ✕ images of TREM2 + cells in the hippocampus of 15-month WT and APP/PS1 rats. C) Quantification of TREM2 cell density in the corpus callosum of 3-, 9-, and 15-month WT and APP/PS1 rats assessed using t -tests. D) Representative 20 ✕ images of TREM2 + cells in the corpus callosum of 15-month WT and APP/PS1 rats. Scale bar indicates 25 μm ∗ Indicates statistical significance ( p < 0.05). Data represent the group mean ± SEM. n = 4 males and 4 females per group.

Article Snippet: Membranes were washed for 3 × 10 min with TBST prior to incubation with anti-mouse (TMEM119, ⍺-tubulin) or anti-rabbit (TREM2) HRP-conjugated secondary antibodies (1:10,000, Jackson Laboratories) for 1 h at room temperature.

Techniques: Expressing

Journal: Brain, Behavior, & Immunity - Health

Article Title: Increased circulating TREM2 + microglial extracellular vesicles in aged APP/PS1 Alzheimer's disease rats

doi: 10.1016/j.bbih.2026.101261

Figure Lengend Snippet: Impaired spatial memory associates with increased TMEM119 + /TREM2 + EVs in 15-month-old rats. A) Simple linear regression between TMEM119 + /TREM2 + events/μl and total RAWM errors in 3-, 9-, and 15-month WT and APP/PS1 rats. n = 10-12 males and females per group.

Article Snippet: Membranes were washed for 3 × 10 min with TBST prior to incubation with anti-mouse (TMEM119, ⍺-tubulin) or anti-rabbit (TREM2) HRP-conjugated secondary antibodies (1:10,000, Jackson Laboratories) for 1 h at room temperature.

Techniques: