ArticlePloS one2015
Oral TNFα Modulation Alters Neutrophil Infiltration, Improves Cognition and Diminishes Tau and Amyloid Pathology in the 3xTgAD Mouse Model.
Article in PloS one, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 33 papers.
What it found
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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.
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Who cites it
33 citing papers in PubMed, 75 citations in OpenAlex.
- The aging gut-glia-immune axis in alzheimer's disease: microbiome-derived mediators of neuroinflammation and therapeutic innovation.GeroScience · 2026Review
- Selective Inhibition of Tumor Necrosis Factor for Attenuating Alzheimer's Disease: Strategies Targeting Neuroinflammation.Inflammation · 2026Review
- The role of peripheral innate immune cells in Alzheimer's disease progression.Frontiers in immunology · 2025Review
- Elucidating Microglial Heterogeneity and Functions in Alzheimer's Disease Using Single-cell Analysis and Convolutional Neural Network Disease Model Construction.Scientific reports · 2024Article
- Transcriptomic Analysis of Lipid Metabolism Genes in Alzheimer's Disease: Highlighting Pathological Outcomes and Compartmentalized Immune Status.Journal of molecular neuroscience : MN · 2024Article
- Immune cells: potential carriers or agents for drug delivery to the central nervous system.Military Medical Research · 2024Review
- Modulation of hippocampal protein expression by a brain penetrant biologic TNF-α inhibitor in the 3xTg Alzheimer's disease mice.Journal of translational medicine · 2024Article
- The innate immune response in tauopathies.European journal of immunology · 2023Review
- Apoptotic cell death in disease-Current understanding of the NCCD 2023.Cell death and differentiation · 2023Review
- Neutrophils as a potential therapeutic target in Alzheimer's disease.Frontiers in immunology · 2023Review
- Efficacy and Safety of a Brain-Penetrant Biologic TNF-α Inhibitor in Aged APP/PS1 Mice.Pharmaceutics · 2022Article
- The Immune System as a Therapeutic Target for Alzheimer's Disease.Life (Basel, Switzerland) · 2022Review
- Microglia: Friend and foe in tauopathy.Progress in neurobiology · 2022Review
- Biologic TNF-α inhibitors reduce microgliosis, neuronal loss, and tau phosphorylation in a transgenic mouse model of tauopathy.Journal of neuroinflammation · 2021Article
- Early neuroinflammation is associated with lower amyloid and tau levels in cognitively normal older adults.Brain, behavior, and immunity · 2021Article
- Repurposing Immunomodulatory Imide Drugs (IMiDs) in Neuropsychiatric and Neurodegenerative Disorders.Frontiers in neuroscience · 2021Review
- A 3'UTR modification of the TNF-α mouse gene increases peripheral TNF-α and modulates the Alzheimer-like phenotype in 5XFAD mice.Scientific reports · 2020Article
- The role of neutrophils in neuro-immune modulation.Pharmacological research · 2020Review
- Neurodegenerative Susceptibility During Maternal Nutritional Programing: Are Central and Peripheral Innate Immune Training Relevant?Frontiers in neuroscience · 2020Review
- Exploiting microglial and peripheral immune cell crosstalk to treat Alzheimer's disease.Journal of neuroinflammation · 2019Review
Corrections and comments
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Authors and funding
9 authors at 3 institutions in 1 country.
Funding
Abstract
Cytokines such as TNFα can polarize microglia/macrophages into different neuroinflammatory types. Skewing of the phenotype towards a cytotoxic state is thought to impair phagocytosis and has been described in Alzheimer's Disease (AD). Neuroinflammation can be perpetuated by a cycle of increasing cytokine production and maintenance of a polarized activation state that contributes to AD progression. In this study, 3xTgAD mice, age 6 months, were treated orally with 3 doses of the TNFα modulating compound isoindolin-1,3 dithione (IDT) for 10 months. We demonstrate that IDT is a TNFα modulating compound both in vitro and in vivo. Following long-term IDT administration, mice were assessed for learning & memory and tissue and serum were collected for analysis. Results demonstrate that IDT is safe for long-term treatment and significantly improves learning and memory in the 3xTgAD mouse model. IDT significantly reduced paired helical filament tau and fibrillar amyloid accumulation. Flow cytometry of brain cell populations revealed that IDT increased the infiltrating neutrophil population while reducing TNFα expression in this population. IDT is a safe and effective TNFα and innate immune system modulator. Thus small molecule, orally bioavailable modulators are promising therapeutics for Alzheimer's disease.
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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.