Complement Receptor 1 / CR1 and Alzheimer's Disease / AD

Top Risk Genes for Alzheimer's Disease / AD (Proteins | Antibodies | Genes | ELISA Kits)

Complement Receptor 1 / CR1 and Alzheimer's Disease Background

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.

Alzheimer's disease (AD) is the most common neurodegenerative disease and it poses an ever-increasing burden to an aging population. Most often, AD is diagnosed in people over 65 years of age, although the less-prevalent early-onset Alzheimer's can occur much earlier. In 2006, there were 26.6 million su$erers worldwide. Alzheimer's disease is predicted to affect 1 in 85 people globally by 2050. 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 Alzheimer's disease (LOAD) is poorly defined genetically, and up until recently the only known risk factor was the ɛ4 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.

Since there is increasing evidence of the involvement of the complement system in AD, an accurate biomarker utilizing this system that has signi"cant diagnostic or predictive value would be an excellent tool for developing and testing novel therapies for the treatment of Alzheimer's disease.

Complement Receptor 1 / CR1 and Alzheimer's Disease References

1. Crehan H, et al. (2012). Complement receptor 1 (CR1) and Alzheimer's disease. Immunobiology, 217(2), 244-250.
2. Carrasquillo M M, et al. (2010). Replication of CLU, CR1, and PICALM associations with alzheimer disease. Archives of neurology, 67(8), 961-964.
3. Brouwers N, et al. (2012). Alzheimer risk associated with a copy number variation in the complement receptor 1 increasing C3b/C4b binding sites. Molecular psychiatry, 17(2), 223-233.
4. Khera R, et al. (2009). Complement receptor 1: disease associations and therapeutic implications. Molecular immunology, 46(5), 761-772.
5. Klickstein L B, et al. (1988). Identification of distinct C3b and C4b recognition sites in the human C3b/C4b receptor (CR1, CD35) by deletion mutagenesis. The Journal of experimental medicine, 168(5), 1699-1717.