ArticleAlzheimer's & dementia : the journal of the Alzheimer's Association2021
Acute systemic inflammation exacerbates neuroinflammation in Alzheimer's disease: IL-1β drives amplified responses in primed astrocytes and neuronal network dysfunction.
Article in Alzheimer's & dementia : the journal of the Alzheimer's Association, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 161 papers, 4 of them syntheses that pooled it.
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Who cites it
161 citing papers in PubMed, 4 syntheses or guidelines pooled it, 259 citations in OpenAlex.
- Perioperative neurofilament light chain and glial fibrillary acidic protein as biomarkers of postoperative delirium: a systematic review and meta-analysis.BMC geriatrics · 2026Pooled it
- Medication-induced causes of delirium in patients with and without dementia: a systematic review of published neurology guidelines.International journal of clinical pharmacy · 2025Pooled it
- The Effects of Different Exercise Interventions on Patients with Subjective Cognitive Decline: A Systematic Review and Network Meta-Analysis.The journal of prevention of Alzheimer's disease · 2024Pooled it
- Risk of Dementia or Cognitive Impairment in Sepsis Survivals: A Systematic Review and Meta-Analysis.Frontiers in aging neuroscience · 2022Pooled it
- MAFG as a Redox-Sensitive Node Linking Peripheral Immune Reprogramming to Cognitive Risk in the Sepsis-to-Alzheimer's Disease Continuum: Single-Cell Dissection and Adoptive-Transfer Validation.CNS neuroscience & therapeutics · 2026Article
- Early amyloid pathology in mice synergistically worsens post-sepsis behavioral impairment and microglial synaptic phagocytosis.Brain, behavior, & immunity - health · 2026Article
- Targeting innovative therapeutic approaches to the hallmarks of aging to combat Alzheimer's disease.Neural regeneration research · 2026Article
- Engineered nanosponges mitigate peripheral stress-induced neuroinflammation and restore cognitive function.bioRxiv : the preprint server for biology · 2026Article
- Chemokines in Alzheimer's Disease: Early Defence, Late Damage and the Impact of Sex and Infection.Basic & clinical pharmacology & toxicology · 2026Review
- Neurodegenerative diseases and immune system: From pathogenic mechanism to therapy.Neural regeneration research · 2026Article
- Lung endothelial cytopathic tau is sufficient to impair long-term potentiation during infection.American journal of respiratory cell and molecular biology · 2026Article
- Prolonged systemic inflammation worsens impairments to astrocyte CaAlzheimer's & dementia : the journal of the Alzheimer's Association · 2026Article
- The roles of microglia and astrocytes in inflammasomes and neurological disorders.Neural regeneration research · 2026Article
- MicroRNA and Alzheimer's disease: Diagnostic biomarkers and potential therapeutic targets.Neural regeneration research · 2026Article
- Review
- Association of Staphylococcus aureus bloodstream infection with 7-day incident delirium in critically Ill adults: a propensity-weighted competing risk analysis.BMC infectious diseases · 2026Article
- Systems biology-based drug repurposing for neuroinflammation treatment in activated human microglia.Scientific reports · 2026Article
- Microglia in systemic neuroimmune communication: functions beyond phagocytosis.Trends in immunology · 2026Review
- Role of aging‑related cytokines in neurodegenerative disease (Review).International journal of molecular medicine · 2026Review
- Characterization of a distinct form of vimentin in the neurodegenerative brain.Acta neuropathologica communications · 2026Article
101 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
16 authors at 3 institutions in 3 countries.
Funding
Abstract
Neuroinflammation contributes to Alzheimer's disease (AD) progression. Secondary inflammatory insults trigger delirium and can accelerate cognitive decline. Individual cellular contributors to this vulnerability require elucidation. Using APP/PS1 mice and AD brain, we studied secondary inflammatory insults to investigate hypersensitive responses in microglia, astrocytes, neurons, and human brain tissue. The NLRP3 inflammasome was assembled surrounding amyloid beta, and microglia were primed, facilitating exaggerated interleukin-1β (IL-1β) responses to subsequent LPS stimulation. Astrocytes were primed to produce exaggerated chemokine responses to intrahippocampal IL-1β. Systemic LPS triggered microglial IL-1β, astrocytic chemokines, IL-6, and acute cognitive dysfunction, whereas IL-1β disrupted hippocampal gamma rhythm, all selectively in APP/PS1 mice. Brains from AD patients with infection showed elevated IL-1β and IL-6 levels. Therefore, amyloid leaves the brain vulnerable to secondary inflammation at microglial, astrocytic, neuronal, and cognitive levels, and infection amplifies neuroinflammatory cytokine synthesis in humans. Exacerbation of neuroinflammation to produce deleterious outcomes like delirium and accelerated disease progression merits careful investigation in humans.
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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.