ArticleActa neuropathologica communications2022
Aβ oligomers trigger necroptosis-mediated neurodegeneration via microglia activation in Alzheimer's disease.
Article in Acta neuropathologica communications, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 50 papers, 1 of them a synthesis 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.
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Who cites it
50 citing papers in PubMed, 1 synthesis or guideline pooled it, 71 citations in OpenAlex.
- Uncovering Necroptosis in Alzheimer's Disease: A Systematic Review of Evidence Across Experimental Models.Cellular and molecular neurobiology · 2025Pooled it
- RIPK1 Links Metabolic Stresses to Inflammatory and Degenerative Pathways in Alzheimer's Disease.Neuroscience bulletin · 2026Article
- Mechanisms, regulation and clinical relevance of necroptosis.Nature reviews. Molecular cell biology · 2026Review
- Review
- Review
- Molecular Mechanisms Underlying Alzheimer's Disease Pathogenesis: Comprehensive Overview.International journal of molecular sciences · 2026Review
- RIPK 1 in Alzheimer's Disease: Research Progress Integrating Pathogenesis on Necroptosis-Related Neuroinflammation, and Potential Therapeutic Strategies.Biomedicines · 2026Review
- Programmed cell death: a promising management for Alzheimer's disease.Apoptosis : an international journal on programmed cell death · 2026Review
- Non-canonical cell death in neurodegeneration: emerging mechanisms and therapeutic Frontiers.Apoptosis : an international journal on programmed cell death · 2026Review
- Advances and Therapeutic Potential of Anthraquinone Compounds in Neurodegenerative Diseases: A Comprehensive Review.Drug design, development and therapy · 2026Review
- PANoptosis in neurological disorders: from inflammatory cell death mechanisms to neuroprotective strategies.Frontiers in neuroscience · 2026Review
- Targeting Microglial Activation to Modulate Neuroinflammation in Alzheimer's Disease.Neuromolecular medicine · 2025Review
- Necroptotic cell death consequences and disease relevance.Nature immunology · 2025Review
- Piperine Prevents Scopolamine-Induced Cognitive Impairment via its Antioxidant and Anti-Inflammatory Roles; Suggesting Potential Modulation of Necroptosis-Related Genes Including MLKL and TNF-α.Journal of molecular neuroscience : MN · 2025Article
- Review
- Role of Necroptosis and Neuroinflammation in CSVD-Associated Cognitive Decline in db/db Mice.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2025Article
- The Therapeutic Potential of Glymphatic System Activity to Reduce the Pathogenic Accumulation of Cytotoxic Proteins in Alzheimer's Disease.International journal of molecular sciences · 2025Review
- The multifaceted roles of apolipoprotein E4 in Alzheimer's disease pathology and potential therapeutic strategies.Cell death discovery · 2025Review
- The Role of S6K1 in Aging and Alzheimer's Disease: Mechanistic Insights and Therapeutic Potential.International journal of molecular sciences · 2025Review
- Harnessing human iPSC-microglia for CNS-wide delivery of disease-modifying proteins.Cell stem cell · 2025Article
Corrections and comments
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Authors and funding
11 authors at 5 institutions in 3 countries.
Funding
Abstract
Alzheimer's disease (AD) is a major adult-onset neurodegenerative condition with no available treatment. Compelling reports point amyloid-β (Aβ) as the main etiologic agent that triggers AD. Although there is extensive evidence of detrimental crosstalk between Aβ and microglia that contributes to neuroinflammation in AD, the exact mechanism leading to neuron death remains unknown. Using postmortem human AD brain tissue, we show that Aβ pathology is associated with the necroptosis effector pMLKL. Moreover, we found that the burden of Aβ oligomers (Aβo) correlates with the expression of key markers of necroptosis activation. Additionally, inhibition of necroptosis by pharmacological or genetic means, reduce neurodegeneration and memory impairment triggered by Aβo in mice. Since microglial activation is emerging as a central driver for AD pathogenesis, we then tested the contribution of microglia to the mechanism of Aβo-mediated necroptosis activation in neurons. Using an in vitro model, we show that conditioned medium from Aβo-stimulated microglia elicited necroptosis in neurons through activation of TNF-α signaling, triggering extensive neurodegeneration. Notably, necroptosis inhibition provided significant neuronal protection. Together, these findings suggest that Aβo-mediated microglia stimulation in AD contributes to necroptosis activation in neurons and neurodegeneration. As necroptosis is a druggable degenerative mechanism, our findings might have important therapeutic implications to prevent the progression of 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.