ArticlePloS one2018
A monoclonal antibody targeting amyloid β (Aβ) restores complement factor I bioactivity: Potential implications in age-related macular degeneration and Alzheimer's disease.
Article in PloS one, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers.
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Who cites it
20 citing papers in PubMed, 34 citations in OpenAlex.
- Age-related macular degeneration and cerebral amyloid angiopathy have similar pathologies from cholesterol-APOE-amyloid-β-complement mediated inflammation.Progress in retinal and eye research · 2026Review
- Hallmarks of aging in age-related macular degeneration and age-related neurological disorders: novel insights into common mechanisms and clinical relevance.Eye (London, England) · 2025Review
- Macular white dot lesions with hyperreflective optical coherence tomography findings in cynomolgus and rhesus monkeys.Molecular vision · 2024Article
- The Relationship between Complements and Age-Related Macular Degeneration and Its Pathogenesis.Journal of ophthalmology · 2024Review
- Review
- Recent Advances in Age-Related Macular Degeneration Therapies.Molecules (Basel, Switzerland) · 2022Review
- Systemic Complement Activation Profiles in Nonexudative Age-Related Macular Degeneration: A Systematic Review.Ophthalmology science · 2022Article
- Systemic Complement Activation Profiles in Nonexudative Age-Related Macular Degeneration: A Meta-Analysis.Journal of clinical medicine · 2022Article
- Neuroinflammation and Hypothalamo-Pituitary Dysfunction: Focus of Traumatic Brain Injury.International journal of molecular sciences · 2021Review
- Role of Retinal Amyloid-β in Neurodegenerative Diseases: Overlapping Mechanisms and Emerging Clinical Applications.International journal of molecular sciences · 2021Review
- Statins in Neuro-ophthalmology.Neuro-ophthalmology (Aeolus Press) · 2021Review
- Retinal biomarkers for Alzheimer's disease and vascular cognitive impairment and dementia (VCID): implication for early diagnosis and prognosis.GeroScience · 2020Review
- Impacts of CR1 genetic variants on cerebrospinal fluid and neuroimaging biomarkers in alzheimer's disease.BMC medical genetics · 2020Article
- Functional Analysis of Rare Genetic Variants in Complement Factor I (Translational vision science & technology · 2020Article
- Rare Genetic Variants in Complement Factor I Lead to Low FI Plasma Levels Resulting in Increased Risk of Age-Related Macular Degeneration.Investigative ophthalmology & visual science · 2020Article
- Review
- Observational
- Plasma biomarkers of the amyloid pathway are associated with geographic atrophy secondary to age-related macular degeneration.PloS one · 2020Article
- Brain-Immune Interactions and Neuroinflammation After Traumatic Brain Injury.Frontiers in neuroscience · 2019Review
- Autoimmune-Mediated Retinopathy in CXCR5-Deficient Mice as the Result of Age-Related Macular Degeneration Associated Proteins Accumulation.Frontiers in immunology · 2019Article
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Authors and funding
7 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Activation of the alternative complement cascade has been implicated in the pathogenesis of age related macular degeneration (AMD) and Alzheimer's disease (AD). Amyloid β (Aβ), a component of drusen, may promote complement activation by inhibiting CFI bioactivity. We determined whether Aβ reduced CFI bioactivity and whether antibodies against Aβ including a monoclonal antibody, GSK933776 could restore CFI bioactivity. We also measured CFI bioactivity in plasma of subjects with AMD and AD. In support of the GSK933776 development program in AMD (geographic atrophy), we developed a quantitative assay to measure CFI bioactivity based on its ability to cleave C3b to iC3b, and repeated it in presence or absence of Aβ and anti-Aβ antibodies. Using this assay, we measured CFI bioactivity in plasma of 194 subjects with AMD, and in samples from subjects with AD that had been treated with GSK933776 as part of the GSK933776 development program in AD. Aβ reduced the CFI bioactivity by 5-fold and pre-incubation with GSK933776 restored CFI bioactivity. In subjects with AMD, plasma CFI levels and bioactivity were not significantly different from non-AMD controls. However, we detected a positive linear trend, suggesting increasing activity with disease severity. In subjects with AD, we observed a 10% and 27% increase in overall CFI bioactivity after treatment with GSK933776 during the second and third dose. Our studies indicate that CFI enzymatic activity can be inhibited by Aβ and be altered in proinflammatory diseases such as AMD and AD, in which deposition of Aβ and activation of the alternative complement cascade are believed to play a key role in the disease process.
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