ArticleActa neuropathologica communications2016
The relationship between complement factor C3, APOE ε4, amyloid and tau in Alzheimer's disease.
Article in Acta neuropathologica communications, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 42 papers, 2 of them syntheses that pooled it.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
42 citing papers in PubMed, 2 syntheses or guidelines pooled it, 69 citations in OpenAlex.
- The complement cascade in Alzheimer's disease: a systematic review and meta-analysis.Molecular psychiatry · 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
- Baseline cerebrospinal fluid complement balance is associated with longitudinal memory decline in relation to plasma p‑tau181 levels in mild cognitive impairment.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2026Article
- The complement system in Alzheimer's disease: evaluating biomarker potential in a complex neuroimmune context.Journal of neuroinflammation · 2026Review
- The complement cascade in Alzheimer's disease: modern implications of an ancient immune protagonist.Molecular neurodegeneration · 2025Review
- APOE-Targeted Therapeutics for Alzheimer's Disease.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2025Review
- 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
- Global C3 lowering in adulthood protects against hippocampal dysfunction and cognitive impairment in aged mice.Research square · 2025Article
- The Effect of APOE ε4 on Alzheimer's Disease Fluid Biomarkers: A Cross-Sectional Study Based on the COAST.CNS neuroscience & therapeutics · 2025Observational
- Plasma Proteomic Biomarkers in Alzheimer's Disease and Cardiovascular Disease: A Longitudinal Study.International journal of molecular sciences · 2024Article
- Subsequent correlated changes in complement component 3 and amyloid beta oligomers in the blood of patients with Alzheimer's disease.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2024Article
- Effects of the active amyloid beta immunotherapy CAD106 on PET measurements of amyloid plaque deposition in cognitively unimpaired APOE ε4 homozygotes.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2024Article
- Associations of cerebrospinal fluid complement proteins with Alzheimer's pathology, cognition, and brain structure in non-dementia elderly.Alzheimer's research & therapy · 2024Article
- The Importance of Complement-Mediated Immune Signaling in Alzheimer's Disease Pathogenesis.International journal of molecular sciences · 2024Review
- Article
- Complement protein levels in serum astrocyte-derived exosomes are associated with cognitive impairment in obstructive sleep apnea.Journal of clinical sleep medicine : JCSM : official publication of the American Academy of Sleep Medicine · 2023Article
- Elevated CSF and plasma complement proteins in genetic frontotemporal dementia: results from the GENFI study.Journal of neuroinflammation · 2022Article
- Apolipoprotein E Proteinopathy Is a Major Dementia-Associated Pathologic Biomarker in Individuals with or without the APOE Epsilon 4 Allele.The American journal of pathology · 2022Article
- Free complement and complement containing extracellular vesicles as potential biomarkers for neuroinflammatory and neurodegenerative disorders.Frontiers in immunology · 2022Review
- Potential Progression Mechanism and Key Genes in Early Stage of mTBI.Evidence-based complementary and alternative medicine : eCAM · 2022Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
4 authors at 2 institutions in 1 country.
Funding
Abstract
Inflammation is becoming increasingly recognized as an important contributor to Alzheimer's disease (AD) pathogenesis. As a part of the innate immune system, the complement cascade enhances the body's ability to destroy and remove pathogens and has recently been shown to influence Alzheimer's associated amyloid and tau pathology. However, little is known in humans about the effects of the complement system and genetic modifiers of AD risk like the ε4 allele of apolioprotein E (APOE ε4) on AD pathobiology. We evaluated cerebrospinal fluid (CSF) protein levels from 267 individuals clinically diagnosed as cognitively normal, mild cognitive impairment, and AD. Using linear models, we assessed the relationship between APOE ε4 genotype, CSF Complement 3 (C3), CSF amyloid-β (amyloid) and CSF hyperphosphorylated tau (ptau). We found a significant interaction between APOE ε4 and CSF C3 on both CSF amyloid and CSF ptau. We also found that CSF C3 is only associated with CSF ptau after accounting for CSF amyloid. Our results support a conceptual model of the AD pathogenic cascade where a synergistic relationship between the complement cascade (C3) and APOE ε4 results in elevated Alzheimer's neurodegeneration and in turn, amyloid further regulates the effect of the complement cascade on downstream tau pathology.
Indexed as
Identifiers
What OpenQuestion holds
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.