Journal: Translational Psychiatry

Article Title: Astrocytic APOE3-Christchurch expression ameliorates brain amyloid-β pathology in 5xFAD mice

doi: 10.1038/s41398-026-04002-9

Figure Lengend Snippet: ( A - C ) Aβ40 and Aβ42 levels in the soluble TBS fractions ( A ), detergent soluble (TBS-X) fractions ( B ), and insoluble neutralized formic acid (FA) fractions ( C ) of cortical brain homogenates in the 5xFAD mice were measured by ELISA at 8 months of age, normalized to protein concentrations of each fraction. ( D ) Soluble oligomeric Aβ (oAβ) levels in the TBS-X fractions of cortical brain homogenates in the 5xFAD mice were measured by ELISA at 8 months of age, normalized to protein concentrations. ( E, F ) Amounts of full-length APP in the TBS-X fractions of mouse cortical lysates were measured by western blot at 8 months of age, normalized to those of β-actin (ACTB). Data are expressed as means ± SEM (GFP: N = 12; APOE3: N = 18; APOE3Ch: N = 13; Open circles: females, closed circles: males). Injection group differences were analyzed using two-way ANOVA, with Tukey’s multiple comparisons test, adjusting for sex. *, P < 0.05; **, P < 0.01.

Article Snippet: Recombinant Aβ42 monomer (1 mg/ml) (Stressmarq, #SPR-485) was incubated at room temperature for 10 min. To dissolve the peptide, 7.5 μl of cold DMSO (Sigma Aldrich) was added, followed by 92.5 μl of cold PBS (PH 7.4) to reach a final concentration of 220 μM monomeric Aβ42.

Techniques: Enzyme-linked Immunosorbent Assay, Western Blot, Injection

Journal: Translational Psychiatry

Article Title: Astrocytic APOE3-Christchurch expression ameliorates brain amyloid-β pathology in 5xFAD mice

doi: 10.1038/s41398-026-04002-9

Figure Lengend Snippet: ( A ) Isogenic iPSC-derived astrocytes (iPSC-ACs) with homozygous APOE3 (left) and APOE3Ch (right) were immunostained for GFAP (green) and S100b (red). DAPI (blue) stains nuclei. Scale bars: 100 µm. ( B ) APOE mRNA levels in the iPSC-ACs were measured by RT-qPCR, normalized to those of β-actin ( ACTB ). ( C, D ) Amounts of APOE in the conditioned medium (CM) from iPSC-ACs were measured by western blot, normalized to protein amounts of cell lysates. ( E ) Effects of the CM from iPSC-ACs on Aβ42 aggregation was assessed by western blot using 6E10 antibody. ( F - G ) Populations of Aβ fibrils (F; > 150 kDa), oligomers (G; 37–150 kDa), and monomers ( H ; < 10 kDa) were quantified. Data expressed as means ± SEM (n = 3–5 independent differentiation batches). Group differences were analyzed using two-tailed student t-test or one-way ANOVA with Tukey’s multiple comparisons test. *, P < 0.05.

Article Snippet: Recombinant Aβ42 monomer (1 mg/ml) (Stressmarq, #SPR-485) was incubated at room temperature for 10 min. To dissolve the peptide, 7.5 μl of cold DMSO (Sigma Aldrich) was added, followed by 92.5 μl of cold PBS (PH 7.4) to reach a final concentration of 220 μM monomeric Aβ42.

Techniques: Derivative Assay, Quantitative RT-PCR, Western Blot, Two Tailed Test

Journal: Frontiers in Pharmacology

Article Title: Pharmacology of nivegacetor (RG6289), a potent and selective gamma secretase modulator in clinical development for the treatment of Alzheimer’s disease

doi: 10.3389/fphar.2026.1783414

Figure Lengend Snippet: Overview of Aβ fragment production following APP processing by BACE1 and gamma secretase, and effects of gamma secretase modulators on Aβ fragment lengths. APP undergoes an initial processing by BACE1 and gamma secretase, producing long precursor peptides of 49 and 48 amino acids length which remain bound to the gamma secretase complex. These precursor peptides undergo exoproteolytic trimming by gamma secretase until they are released as a blend of Aβ fragments with different lengths. Under non-disease conditions the most common fragments are: Aβ40 (∼80%), Aβ42 (∼10%), Aβ38 (∼10%), and Aβ37, and other fragment lengths at very low abundance or under pathological conditions. In the presence of a gamma secretase modulator (GSM) the Aβ peptides remain bound to the gamma secretase enzyme until the trimming has produced shorter fragments sizes, i.e., Aβ38 instead of Aβ42 and Aβ37 instead of Aβ40 is released. Diagram with modifications based on , with information from .

Article Snippet: For the detection of Aβ42, AlphaLISA acceptor beads were coupled with the detection antibody AL12F4 (Covance, Princeton, United States); biotinylated 4G8 antibody was used as a secondary antibody for the detection (BioLegend, San Diego, United States).

Techniques: Produced

Journal: Frontiers in Pharmacology

Article Title: Pharmacology of nivegacetor (RG6289), a potent and selective gamma secretase modulator in clinical development for the treatment of Alzheimer’s disease

doi: 10.3389/fphar.2026.1783414

Figure Lengend Snippet: Dose-dependent modulation of soluble Aβ levels in brain tissue of APPSwe transgenic mice. The levels of Aβ42 (A) , Aβ40 (B) , Aβ37 (C) , Aβ38 (D) , and total Aβ (E) in soluble DEA brain extracts of 5 months old female APPSwe transgenic mice after single oral doses of nivegacetor are shown. The brain drug exposure was measured and correlated with the Aβ42 levels in brain extracts (F) . Each group consists of N = 6 animals, Aβ levels are depicted as percent of Aβ levels in brain extracts from vehicle-treated animals. GSI = MRK-560. Statistical testing by one-way ANOVA, followed by post hoc Dunnett’s comparison test: ** p < 0.01; *** p < 0.001.

Article Snippet: For the detection of Aβ42, AlphaLISA acceptor beads were coupled with the detection antibody AL12F4 (Covance, Princeton, United States); biotinylated 4G8 antibody was used as a secondary antibody for the detection (BioLegend, San Diego, United States).

Techniques: Transgenic Assay, Comparison

Journal: Frontiers in Pharmacology

Article Title: Pharmacology of nivegacetor (RG6289), a potent and selective gamma secretase modulator in clinical development for the treatment of Alzheimer’s disease

doi: 10.3389/fphar.2026.1783414

Figure Lengend Snippet: Aβ42 lowering potency of nivegacetor in the presence or absence of ADAD mutations PSEN1 E280A and PSEN2 N141I. Nivegacetor was tested for its Aβ42 lowering capability in the presence or absence of presenilin mutations, by comparing the potency of nivegacetor measured in H4 APPSwe cells and in H4 APPSwe cells with a targeted disruption of both PSEN1 and PSEN2 genes, transfected with (A) WT PSEN1 and PSEN1 E280A, and with (B) WT PSEN2 and PSEN2 N141I, respectively. For each transfection, a monoclonal stably transfected cell line was generated. Each datapoint represents the mean ± SD of N = 3-7 independent replicates.

Article Snippet: For the detection of Aβ42, AlphaLISA acceptor beads were coupled with the detection antibody AL12F4 (Covance, Princeton, United States); biotinylated 4G8 antibody was used as a secondary antibody for the detection (BioLegend, San Diego, United States).

Techniques: Disruption, Transfection, Stable Transfection, Generated

Journal: RSC Advances

Article Title: Graphene field-effect transistor based multiplexed sensing platform for simultaneous detection of multiple Alzheimer's disease biomarkers

doi: 10.1039/d5ra07384g

Figure Lengend Snippet: The electrical sensing results of GFET biosensor. (a) (PBASE: 5 mM; aptamer: 5 µM). (b) GFET transfer curves for Aβ42 detection under identical functionalization. (c) Four regions functionalized with Aβ42 and hsa-miR-125b aptamers in 1× PBS, with Aβ42 target added for measuring the average signal response at different concentrations. (d) Four regions functionalized with Aβ42 and hsa-miR-125b aptamers in 1× PBS, with hsa-miR-125b target added for measuring the average signal response at different concentrations. (e) The sensor response as a function 125b concentration, with mean, standard deviation, median, and a linear fitting curve. (f) The sensor response as a function Aβ42 concentration, with mean, standard deviation, median, and a linear fitting curve ( n ≥ 13, n is number of sensors used for each measurement) ( n ≥ 13, n is number of sensors used for each measurement).

Article Snippet: Aβ42 and Aβ40 peptides, hsa-miR-125b RNA sequence, the hsa-miR-125b complementary DNA probe and the Aβ42 DNA aptamer were synthesized by Sangon Biotech (Shanghai) Co., Ltd.

Techniques: Concentration Assay, Standard Deviation

Journal: RSC Advances

Article Title: Graphene field-effect transistor based multiplexed sensing platform for simultaneous detection of multiple Alzheimer's disease biomarkers

doi: 10.1039/d5ra07384g

Figure Lengend Snippet: Mixed sample detection results. (a) Higher concentration of Aβ42 biomarker vs. lower concentration of hsa-miR-125b biomarker. The absolute concentrations were (Aβ42 : 125b): 10 pM : 1 fM (10 000 : 1); 50 nM : 50 pM (1000 : 1); and 100 nM : 1 nM (100 : 1). (b) Higher concentration of hsa-miR-125b biomarker vs. lower concentration of Aβ42 biomarker. The absolute concentrations were (125b : Aβ42): 100 nM : 1 fM (10 8 : 1), 100 nM : 1 pM (10 6 : 1), and 50 nM : 50 pM (10 3 : 1). (c) Fixed concentration of Aβ40 biomarker and varying concentrations of hsa-miR-125b ( n ≥ 13, n is number of sensors used for each measurement).

Article Snippet: Aβ42 and Aβ40 peptides, hsa-miR-125b RNA sequence, the hsa-miR-125b complementary DNA probe and the Aβ42 DNA aptamer were synthesized by Sangon Biotech (Shanghai) Co., Ltd.

Techniques: Concentration Assay, Biomarker Discovery

Journal: bioRxiv

Article Title: Reduced LACTB expression in myeloid cells is associated with elevated succinylcarnitine levels and reduced Alzheimer’s disease risk

doi: 10.64898/2026.03.24.711053

Figure Lengend Snippet: A) Diagram summarizing the experimental design for xenotransplantation of human microglia precursors in mice. B) No differences in engraftment between human LACTB KO and WT microglia in hCSF1-5xFAD mice. C) Metabolomics in human LACTB KO or WT microglia isolated from the brains of hCSF1-5xFAD mice (n=2 clones per genotype, 2 mice injected per clone). D) Pathways enriched in GSEA analysis of bulk RNAseq data from human LACTB KO microglia isolated from the brain of hCSF1-5xFAD mice compared to human WT microglia (n=2 clones per genotype, 2 mice injected per clone). E-J) Immunostaining analysis of the number of human microglia (Ku80+Iba1+ cells) associated per plaque (Aβ42) (E), the area covered by plaques and the average plaque size (Aβ42) (F), the plaque compaction (ThioS/MOAB ratio) (G), and the area covered by active (LGALS3 (H), CD9 (I) markers) or antigen-presenting microglia (HLA marker (J)) microglia in hCSF1-5xFAD mice xenotransplanted with LACTB KO or WT human microglia (n=2 clones per genotype, 4-5 mice injected per clone). Graphs display individual data points (left) alongside estimated marginal means with 95% confidence intervals (right). For the raw data dot colors indicate distinct xenotransplanted microglia clones. Statistical details are provided in .

Article Snippet: For additional staining for amyloid pathology, sections were washed again in TBST buffer three times and incubated with the antibody Aβ42 (β-Amyloid clone D54D2 Alexa Fluor 488 Conjugate, Cell Signaling Technologies #51374S, 1:250) overnight; or with Thioflavin S (Sigma-Aldrich #T1892, 1:10,000) for 2 min.

Techniques: Isolation, Clone Assay, Injection, RNA sequencing, Immunostaining, Marker