ArticleProceedings of the National Academy of Sciences of the United States of America2020
Early intraneuronal amyloid triggers neuron-derived inflammatory signaling in APP transgenic rats and human brain.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 70 papers.
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Who cites it
70 citing papers in PubMed, 112 citations in OpenAlex.
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- Retinal proteomics in neurodegeneration: Insights into ocular and brain disorders.Neural regeneration research · 2026Article
- Neuroinflammation in Alzheimer's and Parkinson's diseases: pathogenic mechanisms and therapeutic strategies.Translational neurodegeneration · 2026Review
- Passive amyloid-β immunotherapy in Alzheimer's disease: a multicellular clearance system beyond plaque removal.Molecular neurodegeneration · 2026Review
- Composition and activity of the proteasome in human iPSC-derived neuronal model of early-stage sporadic Alzheimer's disease.bioRxiv : the preprint server for biology · 2026Article
- A lifespan staging model of basal forebrain cholinergic vulnerability.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2026Review
- Intracellular Aβ42 Sequestration by a Serine Protease Mitigates Neurotoxicity in a Drosophila Alzheimer's Disease Model.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Synaptic Plasticity in Neurodegenerative Diseases: Impact of Exercise as Promising Therapeutic Tool.Cells · 2026Review
- Up regulated hippocampal insulin pathway and oxidative stress are related to opposite changes in olfaction and episodic memory in a compensatory metabolic syndrome model in rats.Frontiers in cellular neuroscience · 2026Article
- Identification of a glia-associated amyloid β oligomer subtype and the rescue from reactive astrogliosis by inhibitor NU-9.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2025Article
- TSPO contributes to neuropathology and cognitive deficits in Alzheimer's disease.Journal of neuroinflammation · 2025Article
- Targeting the miR-96-5p/Cathepsin B Pathway to Alleviate Neuron-Derived Neuroinflammation in Alzheimer's Disease.MedComm · 2025Article
- Modulation of neuronal α1-adrenergic receptor reduces tauopathy and neuroinflammation by inhibiting the STING/NF-κB/NLRP3 signaling pathway in Alzheimer's disease mice.Journal of neuroinflammation · 2025Article
- Neuronal and Glial α7 Nicotinic Acetylcholine Receptors: Role in Alzheimer's Disease Pathophysiology.Life (Basel, Switzerland) · 2025Review
- Oxidative Stress: Pathological Driver in Chronic Neurodegenerative Diseases.Antioxidants (Basel, Switzerland) · 2025Review
- Intracellular accumulation of amyloid-ß is a marker of selective neuronal vulnerability in Alzheimer's disease.Nature communications · 2025Article
- Tissue inflammation induced by constitutively active STING is mediated by enhanced TNF signaling.eLife · 2025Article
- Inhibition of amyloid beta oligomer accumulation by NU-9: A unifying mechanism for the treatment of neurodegenerative diseases.Proceedings of the National Academy of Sciences of the United States of America · 2025Article
- Associations between neutrophil-lymphocyte ratio and risk of cognitive impairment among Chinese older adults.BMC geriatrics · 2025Article
- Metal nanoparticles in neuroinflammation: impact on microglial dynamics and CNS function.RSC advances · 2025Review
10 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
8 authors at 6 institutions in 4 countries.
Funding
Abstract
Chronic inflammation during Alzheimer's disease (AD) is most often attributed to sustained microglial activation in response to amyloid-β (Aβ) plaque deposits and cell death. However, cytokine release and microgliosis are consistently observed in AD transgenic animal models devoid of such pathologies, bringing into question the underlying processes that may be at play during the earliest AD-related immune response. We propose that this plaque-independent inflammatory reaction originates from neurons burdened with increasing levels of soluble and oligomeric Aβ, which are known to be the most toxic amyloid species within the brain. Laser microdissected neurons extracted from preplaque amyloid precursor protein (APP) transgenic rats were found to produce a variety of potent immune factors, both at the transcript and protein levels. Neuron-derived cytokines correlated with the extent of microglial activation and mobilization, even in the absence of extracellular plaques and cell death. Importantly, we identified an inflammatory profile unique to Aβ-burdened neurons, since neighboring glial cells did not express similar molecules. Moreover, we demonstrate within disease-vulnerable regions of the human brain that a neuron-specific inflammatory response may precede insoluble Aβ plaque and tau tangle formation. Thus, we reveal the Aβ-burdened neuron as a primary proinflammatory agent, implicating the intraneuronal accumulation of Aβ as a significant immunological component in the AD pathogenesis.
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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.