ArticleProceedings of the National Academy of Sciences of the United States of America2002
Prominent neurodegeneration and increased plaque formation in complement-inhibited Alzheimer's mice.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2002. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 213 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.
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Who cites it
213 citing papers in PubMed, 5 syntheses or guidelines pooled it, 451 citations in OpenAlex.
- Neutrophil to lymphocyte ratio in Alzheimer's disease: A systematic review and meta-analysis.PloS one · 2024Pooled it
- Genome-wide meta-analysis for Alzheimer's disease cerebrospinal fluid biomarkers.Acta neuropathologica · 2022Pooled it
- Association of Peripheral Blood Cell Profile With Alzheimer's Disease: A Meta-Analysis.Frontiers in aging neuroscience · 2022Pooled it
- Genetic Variability in Molecular Pathways Implicated in Alzheimer's Disease: A Comprehensive Review.Frontiers in aging neuroscience · 2021Pooled it
- Understanding AMD by analogy: systematic review of lipid-related common pathogenic mechanisms in AMD, AD, AS and GN.Lipids in health and disease · 2018Pooled it
- Complement component C4 regulates amyloid pathology and glial reactivity in mouse model of Alzheimer's Disease.bioRxiv : the preprint server for biology · 2026Article
- Neurovascular Dysfunction and Glymphatic Impairment: An Unexplored Therapeutic Frontier in Neurodegeneration.International journal of molecular sciences · 2025Review
- LRRK2 deficiency mitigates amyloid β deposition-mediated pathology in a murine Alzheimer's disease model by reprogramming microglia.Translational psychiatry · 2025Article
- Article
- Microglial Drivers of Alzheimer's Disease Pathology: An Evolution of Diverse Participating States.Proteins · 2025Review
- Stroke Exacerbates Respiratory Disorder and Cognition Impairment in Mice with Cerebral Amyloid Angiopathy.Aging and disease · 2025Article
- How the gut microbiota impacts neurodegenerative diseases by modulating CNS immune cells.Journal of neuroinflammation · 2025Review
- Microglia aggregates define distinct immune and neurodegenerative niches in Alzheimer's disease hippocampus.Acta neuropathologica · 2025Article
- Innate Immune Mechanisms in the Central Nervous System.Advances in experimental medicine and biology · 2025Review
- Involvement of Complement in Alzheimer's Disease: From Genetics Through Pathology to Therapeutic Strategies.Current topics in behavioral neurosciences · 2025Review
- The Effect of APOE ε4 on Alzheimer's Disease Fluid Biomarkers: A Cross-Sectional Study Based on the COAST.CNS neuroscience & therapeutics · 2025Observational
- Design, synthesis, and pharmacological evaluation of indazole carboxamides of N-substituted pyrrole derivatives as soybean lipoxygenase inhibitors.Molecular diversity · 2024Article
- Review
- Neuroprotective efficacy of the glucocorticoid receptor modulator PT150 in the rotenone mouse model of Parkinson's disease.Neurotoxicology · 2024Article
- A TrkB and TrkC partial agonist restores deficits in synaptic function and promotes activity-dependent synaptic and microglial transcriptomic changes in a late-stage Alzheimer's mouse model.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2024Article
153 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
7 authors at 4 institutions in 1 country.
Funding
Abstract
Abnormal accumulation of beta-amyloid (Abeta) in Alzheimer's disease (AD) is associated with prominent brain inflammation. Whereas earlier studies concluded that this inflammation is detrimental, more recent animal data suggest that at least some inflammatory processes may be beneficial and promote Abeta clearance. Consistent with these observations, overproduction of transforming growth factor (TGF)-beta1 resulted in a vigorous microglial activation that was accompanied by at least a 50% reduction in Abeta accumulation in human amyloid precursor protein (hAPP) transgenic mice. In a search for inflammatory mediators associated with this reduced pathology, we found that brain levels of C3, the central component of complement and a key inflammatory protein activated in AD, were markedly higher in hAPP/TGF-beta1 mice than in hAPP mice. To assess the importance of complement in the pathogenesis of AD-like disease in mice, we inhibited C3 activation by expressing soluble complement receptor-related protein y (sCrry), a complement inhibitor, in the brains of hAPP mice. Abeta deposition was 2- to 3-fold higher in 1-year-old hAPP/sCrry mice than in age-matched hAPP mice and was accompanied by a prominent accumulation of degenerating neurons. These results indicate that complement activation products can protect against Abeta-induced neurotoxicity and may reduce the accumulation or promote the clearance of amyloid and degenerating neurons. These findings provide evidence for a role of complement and innate immune responses in AD-like disease in mice and support the concept that certain inflammatory defense mechanisms in the brain may be beneficial in neurodegenerative 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 OpenQuestion graph.