ArticleTranslational psychiatry2021
Pro-inflammatory interleukin-6 signaling links cognitive impairments and peripheral metabolic alterations in Alzheimer's disease.
Article in Translational psychiatry, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to 2 registered trials, which are not on this map. Cited by 194 papers, 5 of them syntheses that pooled it.
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.
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.
The Grounded Brain: How Sleeping Grounded (Earthing) Affects Cognition and Personal Perceptions in Participants With Mild Cognitive Impairment Due to Alzheimer's Disease (MCI/AD)
Effect of a Multidomain Intervention Plus Turmeric on the Prevention of Cognitive Decline in People Over 55 Years of Age With Insulin Resistance: A Randomized Clinical Trial
Who cites it
194 citing papers in PubMed, 5 syntheses or guidelines pooled it, 331 citations in OpenAlex.
- Motor performance and its association with Alzheimer's-related biomarkers: a systematic review.Neurological sciences : official journal of the Italian Neurological Society and of the Italian Society of Clinical Neurophysiology · 2026Pooled it
- Association Between Inflammatory Markers and Cognitive Function in Adults With Bipolar Disorder: A Systematic Review.Acta psychiatrica Scandinavica · 2026Pooled it
- Association of IL6 Gene Polymorphisms and Neurological Disorders: Insights from Integrated Bioinformatics and Meta-Analysis.Neuromolecular medicine · 2025Pooled it
- Predictors of cognitive decline in older individuals without dementia: An updated meta-analysis.Annals of clinical and translational neurology · 2023Pooled it
- Association between the neutrophil-to-lymphocyte ratio and cognitive impairment: a meta-analysis of observational studies.Frontiers in endocrinology · 2023Pooled it
- Boswellic acids as an adjunct therapy in Parkinson's disease: a double-blind clinical trial investigating on its effects on motor symptoms and inflammatory markers.Inflammopharmacology · 2025Trial
- Integrating network medicine and foundation models reveals cell-type-specific regulatory alterations in Alzheimer's disease.NAR genomics and bioinformatics · 2026Article
- Virobiome-mediated regulation of microbiota-gut-brain axis signaling and neuroimmune homeostasis.Cell communication and signaling : CCS · 2026Review
- Human amniotic mesenchymal stromal cell-derived extracellular vesicles reprogram microglia and prevent neurodegeneration in experimental models of Alzheimer's disease.Translational neurodegeneration · 2026Article
- Different hypothalamic regions in late-onset Alzheimer's disease and aging: involvement and links with cognitive and non-cognitive features.GeroScience · 2026Article
- Porphyromonas gingivalis Outer Membrane Vesicles-Associated DNA Triggers Inflammation by Inducing IL-6 in Astrocytes.Molecular oral microbiology · 2026Article
- Inflammatory, metabolic, and vascular pathways linking cardiorespiratory fitness to cognition: Results from the IGNITE study.Brain, behavior, & immunity - health · 2026Article
- Interleukin-6 is associated with white matter hyperintensities and cognition independent of Alzheimer's disease plasma biomarkers-HABS-HD.Journal of Alzheimer's disease : JAD · 2026Article
- Article
- Evaluation of serum semaphorin-3A and interleukin 6 levels in patients with neovascular age-related macular degeneration.BMC ophthalmology · 2026Article
- Inflammation profiles in Alzheimer's disease relate to cognition and neurodegeneration.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2026Article
- Review
- Non-receptor tyrosine kinase signaling pathways and therapeutic implications.Signal transduction and targeted therapy · 2026Review
- Chronic central-targeted Interleukin-6 overexpression promotes hippocampal and cortical neuropathology in the Tg2576 mouse model of Alzheimer's disease.Alzheimer's research & therapy · 2026Article
- Microglia regulate adult neurogenesis via interleukin-6Research square · 2026Article
134 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
22 authors at 9 institutions in 4 countries.
Funding
Abstract
Alzheimer's disease (AD) is associated with memory impairment and altered peripheral metabolism. Mounting evidence indicates that abnormal signaling in a brain-periphery metabolic axis plays a role in AD pathophysiology. The activation of pro-inflammatory pathways in the brain, including the interleukin-6 (IL-6) pathway, comprises a potential point of convergence between memory dysfunction and metabolic alterations in AD that remains to be better explored. Using T2-weighted magnetic resonance imaging (MRI), we observed signs of probable inflammation in the hypothalamus and in the hippocampus of AD patients when compared to cognitively healthy control subjects. Pathological examination of post-mortem AD hypothalamus revealed the presence of hyperphosphorylated tau and tangle-like structures, as well as parenchymal and vascular amyloid deposits surrounded by astrocytes. T2 hyperintensities on MRI positively correlated with plasma IL-6, and both correlated inversely with cognitive performance and hypothalamic/hippocampal volumes in AD patients. Increased IL-6 and suppressor of cytokine signaling 3 (SOCS3) were observed in post-mortem AD brains. Moreover, activation of the IL-6 pathway was observed in the hypothalamus and hippocampus of AD mice. Neutralization of IL-6 and inhibition of the signal transducer and activator of transcription 3 (STAT3) signaling in the brains of AD mouse models alleviated memory impairment and peripheral glucose intolerance, and normalized plasma IL-6 levels. Collectively, these results point to IL-6 as a link between cognitive impairment and peripheral metabolic alterations in AD. Targeting pro-inflammatory IL-6 signaling may be a strategy to alleviate memory impairment and metabolic alterations in the 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 Socratic graph.