Complement Receptor 1 (CR1)

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

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. 


External Citations

  1. AlzGene

Further Reading


  1. . Complement receptor 1 (CR1) and Alzheimer's disease. Immunobiology. 2012 Feb;217(2):244-50. Epub 2011 Jul 23 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.