ArticleJournal of neuroinflammation2012
Deficiency of terminal complement pathway inhibitor promotes neuronal tau pathology and degeneration in mice.
Article in Journal of neuroinflammation, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 31 papers, 1 of them a synthesis that pooled it.
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Who cites it
31 citing papers in PubMed, 1 synthesis or guideline pooled it, 51 citations in OpenAlex.
- Transcriptomics Meta-Analysis Reveals Phagosome and Innate Immune System Dysfunction as Potential Mechanisms in the Cortex of Alzheimer's Disease Mouse Strains.Journal of molecular neuroscience : MN · 2023Pooled it
- The complement cascade in Alzheimer's disease: modern implications of an ancient immune protagonist.Molecular neurodegeneration · 2025Review
- Microglial Drivers of Alzheimer's Disease Pathology: An Evolution of Diverse Participating States.Proteins · 2025Review
- Brain-immune interactions: implication for cognitive impairments in Alzheimer's disease and autoimmune disorders.Journal of leukocyte biology · 2024Review
- Age, sex and Alzheimer's disease: a longitudinal study of 3xTg-AD mice reveals sex-specific disease trajectories and inflammatory responses mirrored in postmortem brains from Alzheimer's patients.Alzheimer's research & therapy · 2024Article
- The complement system in neurodegenerative diseases.Clinical science (London, England : 1979) · 2024Article
- The Importance of Complement-Mediated Immune Signaling in Alzheimer's Disease Pathogenesis.International journal of molecular sciences · 2024Review
- Transcriptome analysis reveals genes associated with stem cell activation by physical exercise in the dentate gyrus of aged p16Ink4a knockout mice.Frontiers in cell and developmental biology · 2023Article
- Mechanistic insight into female predominance in Alzheimer's disease based on aberrant protein S-nitrosylation of C3.Science advances · 2022Article
- Alzheimer's disease: Pathophysiology and dental pulp stem cells therapeutic prospects.Frontiers in cell and developmental biology · 2022Review
- Microglia in Alzheimer's Disease: a Key Player in the Transition Between Homeostasis and Pathogenesis.Neurotherapeutics : the journal of the American Society for Experimental NeuroTherapeutics · 2022Review
- Ethanol modulation of cerebellar neuroinflammation in a postnatal mouse model of fetal alcohol spectrum disorders.Journal of neuroscience research · 2021Article
- Deleterious Alteration of Glia in the Brain of Alzheimer's Disease.International journal of molecular sciences · 2020Review
- Neuropathology of the Alzheimer's continuum: an update.Free neuropathology · 2020Article
- Intersection of pathological tau and microglia at the synapse.Acta neuropathologica communications · 2019Review
- Microglia in Alzheimer's disease.The Journal of cell biology · 2018Review
- Molecular Mechanisms of Synaptotoxicity and Neuroinflammation in Alzheimer's Disease.Frontiers in neuroscience · 2018Review
- Microglia Function in the Central Nervous System During Health and Neurodegeneration.Annual review of immunology · 2017Review
- Increased phosphorylation of collapsin response mediator protein-2 at Thr514 correlates with β-amyloid burden and synaptic deficits in Lewy body dementias.Molecular brain · 2016Article
- Changes in the miRNA-mRNA Regulatory Network Precede Motor Symptoms in a Mouse Model of Multiple System Atrophy: Clinical Implications.PloS one · 2016Article
Corrections and comments
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Authors and funding
6 authors at 3 institutions in 1 country.
Funding
Abstract
backgroundThe neuronal microtubule-associated protein tau becomes hyperphosphorylated and forms aggregates in tauopathies but the processes leading to this pathological hallmark are not understood. Because tauopathies are accompanied by neuroinflammation and the complement cascade forms a key innate immune pathway, we asked whether the complement system has a role in the development of tau pathology.
findingsWe tested this hypothesis in two mouse models, which expressed either a central inhibitor of complement or lacked an inhibitor of the terminal complement pathway. Complement receptor-related gene/protein y is the natural inhibitor of the central complement component C3 in rodents. Expressing a soluble variant (sCrry) reduced the number of phospho-tau (AT8 epitope) positive neurons in the brain stem, cerebellum, cortex, and hippocampus of aged P301L mutant tau/sCrry double-transgenic mice compared with tau single-transgenic littermates (JNPL3 line). CD59a is the major inhibitor of formation of the membrane attack complex in mice. Intrahippocampal injection of adeno-associated virus encoding mutant human P301L tau into Cd59a-/- mice resulted in increased numbers of AT8-positive cells compared with wild-type controls. This was accompanied by neuronal and synaptic loss and reduced dendritic integrity.
conclusionsOur data in two independent mouse models with genetic changes in key regulators of the complement system support the hypothesis that the terminal pathway has an active role in the development of tau pathology. We propose that inhibition of the terminal pathway may be beneficial in tauopathies.
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