Journal
ALZHEIMERS & DEMENTIA
Volume 14, Issue 11, Pages 1438-1449Publisher
WILEY
DOI: 10.1016/j.jalz.2018.04.003
Keywords
Complement receptor 1; CR1; Complement C3b/C4b receptor 1; Erythrocyte; Red blood cell; Amyloid beta peptide; Single nucleotide polymorphism; Immune adherence; Clearance
Categories
Funding
- National Institute on Aging of the National Institutes of Health [RO1AG039750, RO1AG07367]
- NIA
- NIH
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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 beta peptide. CR1 SNPs associated with decreased erythrocyte CR1 increased AD risk, whereas a CRI 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. (C) 2018 the Alzheimer's Association. Published by Elsevier Inc. All rights reserved.
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