Alzheimer's disease is associated with low density of the long CR1 isoform

Autor: Jean-Luc Novella, Moustapha Dramé, Bach-Nga Pham, Aymric Kisserli, Valérie Duret, Damien Jolly, Brigitte Reveil, Jacques H. M. Cohen, Béatrice Donvito, Rachid Mahmoudi
Přispěvatelé: UFR de Médecine, Université de Reims Champagne-Ardenne (URCA), Laboratoire de Recherche en Nanosciences - EA 4682 (LRN), Université de Reims Champagne-Ardenne (URCA)-SFR CAP Santé (Champagne-Ardenne Picardie Santé), Université de Reims Champagne-Ardenne (URCA)-Université de Picardie Jules Verne (UPJV)-Université de Reims Champagne-Ardenne (URCA)-Université de Picardie Jules Verne (UPJV)-SFR Condorcet, Université de Reims Champagne-Ardenne (URCA)-Université de Picardie Jules Verne (UPJV)-Centre National de la Recherche Scientifique (CNRS)-Université de Reims Champagne-Ardenne (URCA)-Université de Picardie Jules Verne (UPJV)-Centre National de la Recherche Scientifique (CNRS), Hôpital de Reims - Service de neuro-gériatrie, Hôpital de Reims, Centre Hospitalier Universitaire de Reims (CHU Reims), Hôpital Maison Blanche, Immuno-Régulation dans les Maladies Auto-Immunes Inflammatoires et le Cancer - EA 7509 (IRMAIC), Institut d'Informatique et de Mathématiques Appliquées de Grenoble (IMAG), Université Joseph Fourier - Grenoble 1 (UJF)-Institut National Polytechnique de Grenoble (INPG)-Centre National de la Recherche Scientifique (CNRS), Reims University Hospitals (AOL11UF9156), MAHMOUDI, Rachid
Jazyk: angličtina
Rok vydání: 2015
Předmět:
Risk
Gene isoform
Heterozygote
Aging
Erythrocytes
Complement
Gene Expression
Single-nucleotide polymorphism
Biology
Flow cytometry
CR1 length polymorphism
Western blot
Complement Receptor Type 1
Alzheimer Disease
Polymorphism (computer science)
medicine
Humans
Protein Isoforms
Genetic Predisposition to Disease
Prospective Studies
Allele
CR1
Gene
Alleles
Genetic Association Studies
ComputingMilieux_MISCELLANEOUS
Genetic risk
Polymorphism
Genetic
[SDV.MHEP.GEG] Life Sciences [q-bio]/Human health and pathology/Geriatry and gerontology
medicine.diagnostic_test
General Neuroscience
[SDV.MHEP.GEG]Life Sciences [q-bio]/Human health and pathology/Geriatry and gerontology
Alzheimer's disease
Molecular biology
Phenotype
[SDV.SPEE] Life Sciences [q-bio]/Santé publique et épidémiologie
Receptors
Complement 3b
[SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie
Neurology (clinical)
Geriatrics and Gerontology
Developmental Biology
Zdroj: Neurobiology of Aging
Neurobiology of Aging, Elsevier, 2015, 36 (4), pp.1766.e5-1766.e12. ⟨10.1016/j.neurobiolaging.2015.01.006⟩
Neurobiology of Aging, 2015, 36 (4), pp.1766.e5-1766.e12. ⟨10.1016/j.neurobiolaging.2015.01.006⟩
ISSN: 0197-4580
Popis: 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.
Databáze: OpenAIRE
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