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 - Inserm - Institut national de la santé et de la recherche médicale Accéder directement au contenu
Article Dans Une Revue International Journal of Molecular Sciences Année : 2018

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

Résumé

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.
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Dates et versions

inserm-01851070 , version 1 (29-07-2018)

Identifiants

Citer

Rachid Mahmoudi, Sarah Feldman, Aymric Kisserli, Valérie Duret, Thierry Tabary, et al.. 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. International Journal of Molecular Sciences, 2018, 19 (8), pii: E2175. ⟨10.3390/ijms19082175⟩. ⟨inserm-01851070⟩
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