ArticlePloS one2016
Analysis of the Putative Role of CR1 in Alzheimer's Disease: Genetic Association, Expression and Function.
Article in PloS one, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 67 papers, 4 of them syntheses that pooled it.
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Who cites it
67 citing papers in PubMed, 4 syntheses or guidelines pooled it, 95 citations in OpenAlex.
- Systematic review of human post-mortem immunohistochemical studies and bioinformatics analyses unveil the complexity of astrocyte reaction in Alzheimer's disease.Neuropathology and applied neurobiology · 2022Pooled it
- The complement cascade in Alzheimer's disease: a systematic review and meta-analysis.Molecular psychiatry · 2021Pooled it
- Microglial Phagocytosis: A Disease-Associated Process Emerging from Alzheimer's Disease Genetics.Trends in neurosciences · 2020Pooled it
- Complement receptor 1 genetic polymorphism contributes to sporadic Alzheimer's disease susceptibility in Caucasians: a meta-analysis.Bioscience reports · 2020Pooled it
- Complement component C4 regulates amyloid pathology and glial reactivity in mouse model of Alzheimer's Disease.bioRxiv : the preprint server for biology · 2026Article
- Breaking barriers and beyond: Mechanisms and pathological implications of Zika virus traversal across blood-tissue interfaces.Virologica Sinica · 2026Review
- The complement cascade in Alzheimer's disease: modern implications of an ancient immune protagonist.Molecular neurodegeneration · 2025Review
- fSuSiE enables fine-mapping of QTLs from genome-scale molecular profiles.bioRxiv : the preprint server for biology · 2025Article
- Association of Alzheimer's-Related Gene Variants with Autism Spectrum Disorder: A Case-Control Study in an Iraqi Cohort.Journal of molecular neuroscience : MN · 2025Article
- The blood-brain barriers: novel nanocarriers for central nervous system diseases.Journal of nanobiotechnology · 2025Review
- Proteogenomic analysis of human cerebrospinal fluid identifies neurologically relevant regulation and implicates causal proteins for Alzheimer's disease.Nature genetics · 2024Article
- Brain-immune interactions: implication for cognitive impairments in Alzheimer's disease and autoimmune disorders.Journal of leukocyte biology · 2024Review
- Missense and loss-of-function variants at GWAS loci in familial Alzheimer's disease.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2024Article
- Single cell transcriptomes and multiscale networks from persons with and without Alzheimer's disease.Nature communications · 2024Article
- Immune receptors and aging brain.Bioscience reports · 2024Review
- Role of Crosstalk between Glial Cells and Immune Cells in Blood-Brain Barrier Damage and Protection after Acute Ischemic Stroke.Aging and disease · 2023Review
- Geriatric Surgery Produces a Hypoactive Molecular Phenotype in the Monocyte Immune Gene Transcriptome.Journal of clinical medicine · 2023Article
- Alzheimer's disease-associated complement gene variants influence plasma complement protein levels.Journal of neuroinflammation · 2023Article
- Proteogenomic analysis of human cerebrospinal fluid identifies neurologically relevant regulation and informs causal proteins for Alzheimer's disease.Research square · 2023Article
- Article
7 more citing papers are in PubMed but not listed here.
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Authors and funding
10 authors at 5 institutions in 2 countries.
Funding
Abstract
Chronic activation of the complement system and induced inflammation are associated with neuropathology in Alzheimer's disease (AD). Recent large genome wide association studies (GWAS) have identified single nucleotide polymorphisms (SNPs) in the C3b/C4b receptor (CR1 or CD35) that are associated with late onset AD. Here, anti-CR1 antibodies (Abs) directed against different epitopes of the receptor, were used to localize CR1 in brain, and relative binding affinities of the CR1 ligands, C1q and C3b, were assessed by ELISA. Most Abs tested stained red blood cells in blood vessels but showed no staining in brain parenchyma. However, two monoclonal anti-CR1 Abs labeled astrocytes in all of the cases tested, and this reactivity was preabsorbed by purified recombinant human CR1. Human brain-derived astrocyte cultures were also reactive with both mAbs. The amount of astrocyte staining varied among the samples, but no consistent difference was conferred by diagnosis or the GWAS-identified SNPs rs4844609 or rs6656401. Plasma levels of soluble CR1 did not correlate with diagnosis but a slight increase was observed with rs4844609 and rs6656401 SNP. There was also a modest but statistically significant increase in relative binding activity of C1q to CR1 with the rs4844609 SNP compared to CR1 without the SNP, and of C3b to CR1 in the CR1 genotypes containing the rs6656401 SNP (also associated with the larger isoform of CR1) regardless of clinical diagnosis. These results suggest that it is unlikely that astrocyte CR1 expression levels or C1q or C3b binding activity are the cause of the GWAS identified association of CR1 variants with AD. Further careful functional studies are needed to determine if the variant-dictated number of CR1 expressed on red blood cells contributes to the role of this receptor in the progression of AD, or if another mechanism is involved.
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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.