ArticleMolecular neurodegeneration2012
Hippocampal expression of murine IL-4 results in exacerbation of amyloid deposition.
Article in Molecular neurodegeneration, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 73 papers.
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Who cites it
73 citing papers in PubMed, 114 citations in OpenAlex.
- Low-dose interleukin-2 in patients with mild to moderate Alzheimer's disease: a randomized clinical trial.Alzheimer's research & therapy · 2025Trial
- IL-4 in Alzheimer's Disease-Mechanisms and Therapeutic Potential.Molecular neurobiology · 2026Review
- Role of aging‑related cytokines in neurodegenerative disease (Review).International journal of molecular medicine · 2026Review
- Microglia-astrocyte crosstalk as a key organizing principle of Alzheimer's disease: from homeostatic cooperation to maladaptive signaling loops.Frontiers in aging neuroscience · 2026Review
- Unlocking the potential: advancements and applications of gene therapy in severe disorders.Annals of medicine · 2025Review
- Antagonizing Il10 and Il4 signaling via intracerebral decoy receptor expression attenuates Aβ accumulation.Acta neuropathologica communications · 2025Article
- The role of inhibitory immune checkpoint receptors in the pathogenesis of Alzheimer's disease.Journal of molecular medicine (Berlin, Germany) · 2025Review
- Neuroinflammatory mechanisms may help identify candidate biomarkers in chronic traumatic encephalopathy (CTE).Free neuropathology · 2025Review
- Glyphosate exposure exacerbates neuroinflammation and Alzheimer's disease-like pathology despite a 6-month recovery period in mice.Journal of neuroinflammation · 2024Article
- Article
- Targeting Microglia in Alzheimer's Disease: Pathogenesis and Potential Therapeutic Strategies.Biomolecules · 2024Review
- Type 2 immunity in the brain and brain borders.Cellular & molecular immunology · 2023Review
- Modulation of LPS-Induced Neurodegeneration by Intestinal Helminth Infection in Ageing Mice.International journal of molecular sciences · 2023Article
- How Many Alzheimer-Perusini's Atypical Forms Do We Still Have to Discover?Biomedicines · 2023Review
- Aß Pathology and Neuron-Glia Interactions: A Synaptocentric View.Neurochemical research · 2023Review
- Do Sleep Disturbances have a Dual Effect on Alzheimer's Disease?Cellular and molecular neurobiology · 2023Review
- Microglia-Astrocyte Communication in Alzheimer's Disease.Journal of Alzheimer's disease : JAD · 2023Review
- Non-Pharmacological Therapeutic Options for the Treatment of Alzheimer's Disease.International journal of molecular sciences · 2022Review
- Review
- Intracerebral but Not Peripheral Infection of LiveInternational journal of molecular sciences · 2022Article
13 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
6 authors at 2 institutions in 1 country.
Funding
Abstract
backgroundPro-inflammatory stimuli, including cytokines like Interleukin-1β, Interleukin-6 and Interferon-γ, in the brain have been proposed to exacerbate existing Alzheimer's disease (AD) neuropathology by increasing amyloidogenic processing of APP and promoting further Aβ accumulation in AD. On the other hand, anti-inflammatory cytokines have been suggested to be neuroprotective by reducing neuroinflammation and clearing Aβ. To test this hypothesis, we used adeno-associated virus serotype 1 (AAV2/1) to express an anti-inflammatory cytokine, murine Interleukin-4 (mIL-4), in the hippocampus of APP transgenic TgCRND8 mice with pre-existing plaques.
resultsmIL-4 expression resulted in establishment of an "M2-like" phenotype in the brain and was accompanied by exacerbated Aβ deposition in TgCRND8 mice brains. No change in holo APP or APP C terminal fragment or phosphorylated tau levels were detected in mIL-4 expressing CRND8 cohorts. Biochemical analysis shows increases in both SDS soluble and insoluble Aβ. mIL-4 treatment attenuates soluble Aβ40 uptake by microglia but does not affect aggregated Aβ42 internalization by microglia or soluble Aβ40 internalization by astrocytes.
conclusionsShort term focal mIL-4 expression in the hippocampus leads to exacerbation of amyloid deposition in vivo, possibly mediated by acute suppression of glial clearance mechanisms. Given that recent preclinical data from independent groups indicate engagement of the innate immune system early on during disease pathogenesis may be beneficial, our present study strongly argues for a cautious re-examination of unwarranted side-effects of anti-inflammatory therapies for neurodegenerative diseases, including AD.
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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.