ArticleEMBO reports2023
Reduced binding of apoE4 to complement factor H promotes amyloid-β oligomerization and neuroinflammation.
Article in EMBO reports, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 papers.
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Who cites it
19 citing papers in PubMed, 25 citations in OpenAlex.
- Early binding of anti-amyloid antibodies to CAA drives complement activation, inflammation and ARIA in mice.Molecular neurodegeneration · 2026Article
- Discovery-Driven Plasma Proteomics Identifies a Multi-Protein Signature for Amyloid PET Positivity: A Machine Learning Analysis of the Bio-Hermes Cohort.International journal of molecular sciences · 2026Article
- Innate Immune Evasion of Lyme Disease Pathogen Drives Alzheimer-Like Pathology.Research square · 2026Article
- Early Binding of Anti-Amyloid Antibodies to CAA Drives Complement Activation, Inflammation and ARIA in Mice.bioRxiv : the preprint server for biology · 2026Article
- The dysregulation of innate immunity by Porphyromonas gingivalis in the etiology of Alzheimer's disease.Journal of internal medicine · 2026Review
- Article
- Microglial pathological synaptic pruning in epilepsy: pathophysiology and therapeutic potential.Frontiers in immunology · 2026Review
- Deletion of the Mouse Homolog of Human FHR1 (muFHR1) Alleviates Atherosclerosis in ApoE-/- mice.International journal of medical sciences · 2026Article
- Role of apolipoprotein E4 in alzheimer's disease pathogenesis and emerging therapeutic strategies.Metabolic brain disease · 2025Review
- Lipopolysaccharide clustering in colistin persistent and resistant bacteria.npj antimicrobials and resistance · 2025Article
- Redox modulation of the complement cascade contributes to synapse loss in Alzheimer's disease.Neurotherapeutics : the journal of the American Society for Experimental NeuroTherapeutics · 2025Review
- Genetic Loci Associated With Periodontitis: The FinnGen Study Based on National Health Registers.Journal of clinical periodontology · 2025Article
- Exploring the intersection of atherosclerosis and Alzheimer's disease: the role of inflammation and complement activation.Inflammation research : official journal of the European Histamine Research Society ... [et al.] · 2025Review
- The Alzheimer's disease-associated complement receptor 1 variant confers risk by impacting glial phagocytosis.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2025Article
- ATP11B Modulates Microglial Lipid Metabolism and Alleviates Alzheimer's Disease Pathology.MedComm · 2025Article
- 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
- From Genetics to Neuroinflammation: The Impact of ApoE4 on Microglial Function in Alzheimer's Disease.Cells · 2025Review
- Moss-produced human complement factor H with modified glycans has an extended half-life and improved biological activity.Frontiers in immunology · 2024Article
- Reduced binding of apoE4 to complement factor H promotes amyloid-β oligomerization and neuroinflammation.EMBO reports · 2023Article
Corrections and comments
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Authors and funding
24 authors at 6 institutions in 5 countries.
Funding
Abstract
The APOE4 variant of apolipoprotein E (apoE) is the most prevalent genetic risk allele associated with late-onset Alzheimer's disease (AD). ApoE interacts with complement regulator factor H (FH), but the role of this interaction in AD pathogenesis is unknown. Here we elucidate the mechanism by which isoform-specific binding of apoE to FH alters Aβ1-42-mediated neurotoxicity and clearance. Flow cytometry and transcriptomic analysis reveal that apoE and FH reduce binding of Aβ1-42 to complement receptor 3 (CR3) and subsequent phagocytosis by microglia which alters expression of genes involved in AD. Moreover, FH forms complement-resistant oligomers with apoE/Aβ1-42 complexes and the formation of these complexes is isoform specific with apoE2 and apoE3 showing higher affinity to FH than apoE4. These FH/apoE complexes reduce Aβ1-42 oligomerization and toxicity, and colocalize with complement activator C1q deposited on Aβ plaques in the brain. These findings provide an important mechanistic insight into AD pathogenesis and explain how the strongest genetic risk factor for AD predisposes for neuroinflammation in the early stages of the disease pathology.
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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.