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Complement Receptor 1 (CR1)

Synonyms: Complement component (3b/4b) receptor 1, CD35 antigen, C3b/C4b receptor, C3-binding protein, Knops blood group antigen

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The complement receptor 1 (CR1) gene encodes a transmembrane glycoprotein that functions in the innate immune system. CR1 is expressed on blood cells and microglia. As a receptor for the complement components C3b and C4b, CR1 helps regulate activation of the complement cascade and promotes phagocytosis of immune complexes and cellular debris, as well as Aβ. CR1 attracted attention in Alzheimer’s research when variants at the CR1 locus proved to be associated with risk of late-onset Alzheimer’s disease. Meta-analysis has confirmed several disease-associated single nucleotide polymorphisms (SNPs), as well as a copy-number variation (CNV). CR1 currently ranks among the top 10 risk genes on AlzGene. At least one risk SNP is also linked to intracerebral hemorrhage associated with cerebral amyloid angiopathy (CAA).

While the molecular underpinnings of CR1’s role in AD pathogenesis are not yet clear, accumulating evidence suggests a dysregulation of complement with effects on inflammation and amyloid accumulation. Clinically, a CR1 risk allele has been associated with faster cognitive decline and greater neuropathology burden in longitudinal aging cohorts. 

References

External Citations

  1. AlzGene

Further Reading

News

  1. Complement Receptor Found to Regulate Adult Neurogenesis
  2. San Diego: MHC Class I and Complement—Holding Down Second Jobs in the Synapse
  3. Complement: AD Friend or Foe? New Work Tips Balance to Former
  4. Barcelona: What Lies Beyond Genomewide Association Studies?
  5. Paper Alert: Does the Complement Devour Synapses?
  6. Complement Receptor Found to Regulate Adult Neurogenesis
  7. Repeat Offenders—CLU, CR1, PICALM Hold Up in Association Studies
  8. Vienna: In Genetics, Bigger Is Better—Data Sharing Nets Three New Hits
  9. Vienna: New Genes, Anyone? ICAD Saves Best for Last

Papers

  1. . Complement receptor 1 (CR1) and Alzheimer's disease. Immunobiology. 2012 Feb;217(2):244-50. PubMed.
  2. . Relationship between genetic risk factors and markers for Alzheimer's disease pathology. Biomark Med. 2012 Aug;6(4):477-95. PubMed.
  3. . Genetic insights in Alzheimer's disease. Lancet Neurol. 2013 Jan;12(1):92-104. PubMed.
  4. . Replication of CLU, CR1, and PICALM associations with alzheimer disease. Arch Neurol. 2010 Aug;67(8):961-4. PubMed.