ArticleJournal of neuroinflammation2022
Gas6 induces inflammation and reduces plaque burden but worsens behavior in a sex-dependent manner in the APP/PS1 model of Alzheimer's disease.
Article in Journal of neuroinflammation, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 21 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
21 citing papers in PubMed, 52 citations in OpenAlex.
- Article
- Microglial CD31 suppresses Aβ clearance and promotes Alzheimer pathology in 5×FAD mice.Nature communications · 2026Article
- TYRO3, AXL, MERTK and Their Ligands in Brain Metastases From Colorectal Cancers.Cancer medicine · 2026Article
- Dysregulated Resolution of Inflammation After Respiratory Viral Infections: Molecular Pathways Linking Neuroinflammation to Post-Viral Neuropathic Pain-A Narrative Review.International journal of molecular sciences · 2025Review
- C9orf72 hexanucleotide repeat expansions impair microglial response in ALS.Nature neuroscience · 2025Article
- Single-cell Analysis of Intracellular Transport and Expression of Cell Surface Proteins.bioRxiv : the preprint server for biology · 2025Article
- Altered immune response is associated with sex difference in vulnerability to Alzheimer's disease in human prefrontal cortex.Brain pathology (Zurich, Switzerland) · 2025Article
- The Auditory Brainstem Response Diagnoses Alzheimer-Like Disease in the 5xFAD Mouse Model.eNeuro · 2025Article
- Synthesizing network pharmacology, bioinformatics, and in vitro experimental verification to screen candidate targets of Salidroside for mitigating Alzheimer's disease.Naunyn-Schmiedeberg's archives of pharmacology · 2025Article
- Vitamin K Properties in Stroke and Alzheimer's Disease: A Janus Bifrons in Protection and Prevention.Molecules (Basel, Switzerland) · 2025Review
- The Neuroprotective Effect of Neural Cell Adhesion Molecule L1 in the Hippocampus of Aged Alzheimer's Disease Model Mice.Biomedicines · 2024Article
- An overview on microglial origin, distribution, and phenotype in Alzheimer's disease.Journal of cellular physiology · 2024Review
- Surface protein profiling and subtyping of extracellular vesicles in body fluids reveals non-CSF biomarkers of Alzheimer's disease.Journal of extracellular vesicles · 2024Article
- An exhausted-like microglial population accumulates in aged and APOE4 genotype Alzheimer's brains.Immunity · 2024Article
- Treatment of vascular dementia in female rats with AV-001, an Angiopoietin-1 mimetic peptide, improves cognitive function.Frontiers in neuroscience · 2024Article
- Correction: Gas6 induces infammation and reduces plaque burden but worsens behavior in a sex-dependent manner in the APP/PS1 model of Alzheimer's disease.Journal of neuroinflammation · 2023Article
- Innate Immunity and Sex: Distinct Inflammatory Profiles Associated with Murine Pain in Acute Synovitis.Cells · 2023Article
- iTRAQ-Based Proteomic Analysis of APP Transgenic Mouse Urine Exosomes.International journal of molecular sciences · 2022Article
- Myelin repair in Alzheimer's disease: a review of biological pathways and potential therapeutics.Translational neurodegeneration · 2022Review
- Repopulated microglia induce expression of Cxcl13 with differential changes in Tau phosphorylation but do not impact amyloid pathology.Journal of neuroinflammation · 2022Article
Corrections and comments
- Erratum issued
Authors and funding
8 authors at 2 institutions in 1 country.
Funding
Abstract
backgroundAlzheimer's disease is the leading cause of dementia worldwide. TAM receptor tyrosine kinases (Tyro3, Axl, MerTK) are known for their role in engagement of phagocytosis and modulation of inflammation, and recent evidence suggests a complex relationship between Axl, Mer, and microglial phagocytosis of amyloid plaques in AD. Gas6, the primary CNS TAM ligand, reduces neuroinflammation and improves outcomes in murine models of CNS disease. Therefore, we hypothesized that AAV-mediated overexpression of Gas6 would alleviate plaque pathology, reduce neuroinflammation, and improve behavior in the APP/PS1 model of Alzheimer's disease.
methodsAdeno-associated viral vectors were used to overexpress Gas6 in the APP/PS1 model of Alzheimer's disease. Nine-month-old male and female APP/PS1 and nontransgenic littermates received bilateral stereotactic hippocampal injections of AAV-Gas6 or AAV-control, which expresses a non-functional Gas6 protein. One month after injections, mice underwent a battery of behavioral tasks to assess cognitive function and brains were processed for immunohistochemical and transcriptional analyses.
resultsGas6 overexpression reduced plaque burden in male APP/PS1 mice. However, contrary to our hypothesis, Gas6 increased pro-inflammatory microglial gene expression and worsened contextual fear conditioning compared to control-treated mice. Gas6 overexpression appeared to have no effect on phagocytic mechanisms in vitro or in vivo as measured by CD68 immunohistochemistry, microglial methoxy-04 uptake, and primary microglial uptake of fluorescent fibrillar amyloid beta.
conclusionOur data describes a triad of worsened behavior, reduced plaque number, and an increase in proinflammatory signaling in a sex-specific manner. While Gas6 has historically induced anti-inflammatory signatures in the peripheral nervous system, our data suggest an alternative, proinflammatory role in the context of Alzheimer's disease pathology.
Indexed as
Identifiers
What OpenQuestion holds
Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.