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Int. J. Mol. Sci. 2018, 19(8), 2175; https://doi.org/10.3390/ijms19082175

Inherited and Acquired Decrease in Complement Receptor 1 (CR1) Density on Red Blood Cells Associated with High Levels of Soluble CR1 in Alzheimer’s Disease

1
Department of Internal Medicine and Geriatrics, Reims University Hospitals, Maison Blanche Hospital, 45 rue cognac Jay, 51092 Reims, France
2
Faculty of Medicine, University of Reims Champagne-Ardenne, EA 3797, 51092 Reims, France
3
Institut National de la Santé et de la Recherche Médicale (INSERM), Centre de Recherche des Cordeliers, UMR 1138 Equipe 22, Paris Descartes, Sorbonne Paris Cité University, 75006 Paris, France
4
Department of Medical Informatics, Necker-Enfants Malades Hospital, Assistance Publique des Hôpitaux de Paris (AP-HP), 75015 Paris, France
5
Department of Immunology, Reims University Hospitals, Robert Debré Hospital, 51092 Reims, France
6
Faculty of Medicine, University of Reims Champagne-Ardenne, LRN EA 4682, 51092 Reims, France
7
Department of Research and Innovation, Reims University Hospitals, Robert Debré Hospital, 51092 Reims, France
*
Author to whom correspondence should be addressed.
Received: 30 June 2018 / Revised: 22 July 2018 / Accepted: 23 July 2018 / Published: 25 July 2018
(This article belongs to the Special Issue Molecular Mechanism of Alzheimer's Disease)
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Abstract

The complement receptor 1 (CR1) gene was shown to be involved in Alzheimer’s disease (AD). We previously showed that AD is associated with low density of the long CR1 isoform, CR1*2 (S). Here, we correlated phenotype data (CR1 density per erythrocyte (CR1/E), blood soluble CR1 (sCR1)) with genetic data (density/length polymorphisms) in AD patients and healthy controls. CR1/E was enumerated using flow cytometry, while sCR1 was quantified by ELISA. CR1 polymorphisms were assessed using restriction fragment length polymorphism (RFLP), pyrosequencing, and high-resolution melting PCR. In AD patients carrying the H allele (HindIII polymorphism) or the Q allele (Q981H polymorphism), CR1/E was significantly lower when compared with controls carrying the same alleles (p < 0.01), contrary to sCR1, which was significantly higher (p < 0.001). Using multivariate analysis, a reduction of 6.68 units in density was associated with an increase of 1% in methylation of CR1 (estimate −6.68; 95% confidence intervals (CIs) −12.37, −0.99; p = 0.02). Our data show that, in addition to inherited genetic factors, low density of CR1/E is also acquired. The involvement of CR1 in the pathogenesis of AD might be linked to insufficient clearance of amyloid deposits. These findings may open perspectives for new therapeutic strategies in AD. View Full-Text
Keywords: Alzheimer’s disease; complement receptor 1; CR1 length polymorphism; CR1 density; complement C3b/C4b receptor; complement; dementia; molecular biology; neurosciences; genetic risk Alzheimer’s disease; complement receptor 1; CR1 length polymorphism; CR1 density; complement C3b/C4b receptor; complement; dementia; molecular biology; neurosciences; genetic risk
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Mahmoudi, R.; Feldman, S.; Kisserli, A.; Duret, V.; Tabary, T.; Bertholon, L.-A.; Badr, S.; Nonnonhou, V.; Cesar, A.; Neuraz, A.; Novella, J.L.; Cohen, J.H.M. Inherited and Acquired Decrease in Complement Receptor 1 (CR1) Density on Red Blood Cells Associated with High Levels of Soluble CR1 in Alzheimer’s Disease. Int. J. Mol. Sci. 2018, 19, 2175.

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