title: Alzheimer's disease is associated with low density of the long CR1 isoform.
abstract: The long complement receptor type 1 (CR1) isoform, CR1*2 (S), has been identified as being associated with Alzheimer's disease (AD) risk. We aimed to analyze the phenotypic structural and expression aspects (length and density) of CR1 in erythrocytes of 135 Caucasian subjects (100 AD and 35 controls). CR1 length polymorphism was assessed at protein and gene levels using Western blot and high-resolution melting, respectively. CR1 sites on erythrocytes were enumerated by flow cytometry. CR1 gene analysis, spotting the rs6656401 and rs3818361 polymorphisms, was performed by pyrosequencing. The CR1 density was significantly lower in AD patients expressing the CR1*2 isoform compared with the controls (p = 0.001), demonstrating lower expression of CR1 in CR1*2 carriers. Our data suggested the existence of silent CR1 alleles. Finally, rs6656401 and rs3818361 were strongly associated with CR1 length polymorphism (p < 0.0001). These observations indicate that AD susceptibility is associated with the long CR1 isoform (CR1*2), albeit at a lower density, suggesting that AD results from insufficient clearance of plaque deposits rather than increased inflammation.
authors: Champagne-Ardenne Resource and Research Memory Center (CMRR), Maison Blanche Hospital, Reims University Hospitals, Reims, France; Department of Internal Medicine and Geriatrics, Maison Blanche Hospital, Reims University Hospitals, Reims, France; Faculty of Medicine, University of Reims Champagne-Ardenne, EA 3797, Reims, France. Electronic address: rmahmoudi@chu-reims.fr.
authors: Rachid
authors: R
authors: Mahmoudi
authors: Department of Immunology, Robert Debré Hospital, Reims University Hospitals, Reims, France; Faculty of Medicine, University of Reims Champagne-Ardenne, LRN EA 4682, Reims, France.
authors: Aymric
authors: A
authors: Kisserli
authors: Champagne-Ardenne Resource and Research Memory Center (CMRR), Maison Blanche Hospital, Reims University Hospitals, Reims, France; Department of Internal Medicine and Geriatrics, Maison Blanche Hospital, Reims University Hospitals, Reims, France; Faculty of Medicine, University of Reims Champagne-Ardenne, EA 3797, Reims, France.
authors: Jean-Luc
authors: JL
authors: Novella
authors: Department of Immunology, Robert Debré Hospital, Reims University Hospitals, Reims, France; Faculty of Medicine, University of Reims Champagne-Ardenne, LRN EA 4682, Reims, France.
authors: Béatrice
authors: B
authors: Donvito
authors: Faculty of Medicine, University of Reims Champagne-Ardenne, EA 3797, Reims, France; Department of Research and Innovation, Robert Debré Hospital, Reims University Hospitals, Reims, France.
authors: Moustapha
authors: M
authors: Dramé
authors: Department of Immunology, Robert Debré Hospital, Reims University Hospitals, Reims, France; Faculty of Medicine, University of Reims Champagne-Ardenne, LRN EA 4682, Reims, France.
authors: Brigitte
authors: B
authors: Réveil
authors: Department of Immunology, Robert Debré Hospital, Reims University Hospitals, Reims, France; Faculty of Medicine, University of Reims Champagne-Ardenne, LRN EA 4682, Reims, France.
authors: Valérie
authors: V
authors: Duret
authors: Faculty of Medicine, University of Reims Champagne-Ardenne, EA 3797, Reims, France; Department of Research and Innovation, Robert Debré Hospital, Reims University Hospitals, Reims, France.
authors: Damien
authors: D
authors: Jolly
authors: Department of Immunology, Robert Debré Hospital, Reims University Hospitals, Reims, France; Faculty of Medicine, University of Reims Champagne-Ardenne, LRN EA 4682, Reims, France.
authors: Bach-Nga
authors: BN
authors: Pham
authors: Department of Immunology, Robert Debré Hospital, Reims University Hospitals, Reims, France; Faculty of Medicine, University of Reims Champagne-Ardenne, LRN EA 4682, Reims, France.
authors: Jacques H
authors: JH
authors: Cohen
mesh_terms: D000483:Alleles; D000544:Alzheimer Disease / Q000235:genetics*; D004912:Erythrocytes / Q000378:metabolism; D015870:Gene Expression; D056726:Genetic Association Studies; D020022:Genetic Predisposition to Disease / Q000235:genetics; D006579:Heterozygote; D006801:Humans; D010641:Phenotype; D011110:Polymorphism, Genetic; D011446:Prospective Studies; D020033:Protein Isoforms; D017463:Receptors, Complement 3b / Q000097:blood / Q000737:chemistry* / Q000235:genetics*; D012306:Risk
chemical_list: C509991:CR1 protein, human; D020033:Protein Isoforms; D017463:Receptors, Complement 3b
keywords: Alzheimer's disease; CR1; CR1 length polymorphism; Complement; Genetic risk; Single-nucleotide polymorphism