Complement receptor 1 (CR1) and Alzheimer's disease

Immunobiology. 2012 Feb;217(2):244-50. doi: 10.1016/j.imbio.2011.07.017. Epub 2011 Jul 23.


Alzheimer's disease (AD) is the most common neurodegenerative disease and it poses an ever-increasing burden to an aging population. Several loci responsible for the rare, autosomal dominant form of AD have been identified (APP, PS1 and PS2), and these have facilitated the development of the amyloid cascade hypothesis of AD aetiology. The late onset form of the disease (LOAD) is poorly defined genetically, and up until recently the only known risk factor was the ε4 allele of APOE. Recent genome-wide association studies (GWAS) have identified common genetic variants that increase risk of LOAD. Two of the genes highlighted in these studies, CLU and CR1, suggest a role for the complement system in the aetiology of AD. In this review we analyse the evidence for an involvement of complement in AD. In particular we focus on one gene, CR1, and its role in the complement cascade. CR1 is a receptor for the complement fragments C3b and C4b and is expressed on many different cell types, particularly in the circulatory system. We look at the evidence for genetic polymorphisms in the gene and the possible physiological effects of these well-documented changes. Finally, we discuss the possible impact of CR1 genetic polymorphisms in relation to the amyloid cascade hypothesis of AD and the way in which CR1 may lead to AD pathogenesis.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Alzheimer Disease / genetics*
  • Alzheimer Disease / immunology*
  • Alzheimer Disease / pathology
  • Clusterin / genetics
  • Clusterin / immunology
  • Genetic Predisposition to Disease
  • Genetic Variation
  • Humans
  • Plaque, Amyloid / genetics
  • Plaque, Amyloid / immunology
  • Polymorphism, Genetic
  • Polymorphism, Single Nucleotide
  • Receptors, Complement 3b / genetics
  • Receptors, Complement 3b / immunology*


  • CLU protein, human
  • CR1 protein, human
  • Clusterin
  • Receptors, Complement 3b