Peripheral complement interactions with amyloid β peptide in Alzheimer's disease: Polymorphisms, structure, and function of complement receptor 1

Jenny U. Johansson, William D. Brubaker, Harold Javitz, Andrew W. Bergen, Denise Nishita, Abhishek Trigunaite, Andrés Crane, Justine Ceballos, Diego Mastroeni, Andrea J. Tenner, Marwan Sabbagh, Joseph Rogers

Research output: Contribution to journalArticle

9 Scopus citations

Abstract

Introduction: Genome-wide association studies consistently show that single nucleotide polymorphisms (SNPs) in the complement receptor 1 (CR1) gene modestly but significantly alter Alzheimer's disease (AD) risk. Follow-up research has assumed that CR1 is expressed in the human brain despite a paucity of evidence for its function there. Alternatively, erythrocytes contain >80% of the body's CR1, where, in primates, it is known to bind circulating pathogens. Methods: Multidisciplinary methods were employed. Results: Conventional Western blots and quantitative polymerase chain reaction failed to detect CR1 in the human brain. Brain immunohistochemistry revealed only vascular CR1. By contrast, erythrocyte CR1 immunoreactivity was readily observed and was significantly deficient in AD, as was CR1-mediated erythrocyte capture of circulating amyloid β peptide. CR1 SNPs associated with decreased erythrocyte CR1 increased AD risk, whereas a CR1 SNP associated with increased erythrocyte CR1 decreased AD risk. Discussion: SNP effects on erythrocyte CR1 likely underlie the association of CR1 polymorphisms with AD risk.

Original languageEnglish (US)
Pages (from-to)1438-1449
Number of pages12
JournalAlzheimer's and Dementia
Volume14
Issue number11
DOIs
StatePublished - Nov 2018

Keywords

  • Amyloid β peptide
  • CR1
  • Clearance
  • Complement C3b/C4b receptor 1
  • Complement receptor 1
  • Erythrocyte
  • Immune adherence
  • Red blood cell
  • Single nucleotide polymorphism

ASJC Scopus subject areas

  • Epidemiology
  • Health Policy
  • Developmental Neuroscience
  • Clinical Neurology
  • Geriatrics and Gerontology
  • Psychiatry and Mental health
  • Cellular and Molecular Neuroscience

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    Johansson, J. U., Brubaker, W. D., Javitz, H., Bergen, A. W., Nishita, D., Trigunaite, A., Crane, A., Ceballos, J., Mastroeni, D., Tenner, A. J., Sabbagh, M., & Rogers, J. (2018). Peripheral complement interactions with amyloid β peptide in Alzheimer's disease: Polymorphisms, structure, and function of complement receptor 1. Alzheimer's and Dementia, 14(11), 1438-1449. https://doi.org/10.1016/j.jalz.2018.04.003