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 language | English (US) |
|---|---|
| Journal | Alzheimer's and Dementia |
| DOIs | |
| State | Accepted/In press - Jan 1 2018 |
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Keywords
- Amyloid β peptide
- Clearance
- Complement C3b/C4b receptor 1
- Complement receptor 1
- CR1
- Erythrocyte
- Immune adherence
- Red blood cell
- Single nucleotide polymorphism
ASJC Scopus subject areas
- Epidemiology
- Health Policy
- Developmental Neuroscience
- Clinical Neurology
- Geriatrics and Gerontology
- Cellular and Molecular Neuroscience
- Psychiatry and Mental health
Cite this
Peripheral complement interactions with amyloid β peptide in Alzheimer's disease : Polymorphisms, structure, and function of complement receptor 1. / Johansson, Jenny U.; Brubaker, William D.; Javitz, Harold; Bergen, Andrew W.; Nishita, Denise; Trigunaite, Abhishek; Crane, Andrés; Ceballos, Justine; Mastroeni, Diego; Tenner, Andrea J.; Sabbagh, Marwan; Rogers, Joseph.
In: Alzheimer's and Dementia, 01.01.2018.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Peripheral complement interactions with amyloid β peptide in Alzheimer's disease
T2 - Polymorphisms, structure, and function of complement receptor 1
AU - Johansson, Jenny U.
AU - Brubaker, William D.
AU - Javitz, Harold
AU - Bergen, Andrew W.
AU - Nishita, Denise
AU - Trigunaite, Abhishek
AU - Crane, Andrés
AU - Ceballos, Justine
AU - Mastroeni, Diego
AU - Tenner, Andrea J.
AU - Sabbagh, Marwan
AU - Rogers, Joseph
PY - 2018/1/1
Y1 - 2018/1/1
N2 - 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.
AB - 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.
KW - Amyloid β peptide
KW - Clearance
KW - Complement C3b/C4b receptor 1
KW - Complement receptor 1
KW - CR1
KW - Erythrocyte
KW - Immune adherence
KW - Red blood cell
KW - Single nucleotide polymorphism
UR - http://www.scopus.com/inward/record.url?scp=85049838666&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85049838666&partnerID=8YFLogxK
U2 - 10.1016/j.jalz.2018.04.003
DO - 10.1016/j.jalz.2018.04.003
M3 - Article
C2 - 29792870
AN - SCOPUS:85049838666
JO - Alzheimer's and Dementia
JF - Alzheimer's and Dementia
SN - 1552-5260
ER -