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

Mahmoudi, Rachid; Kisserli, Aymric; Novella, Jean‐Luc; Donvito, Béatrice; Dramé, Moustapha; Réveil, Brigitte; Duret, Valérie; Jolly, Damien; Pham, Bach-Nga; Cohen, Jacques H. M.

doi:10.1016/j.neurobiolaging.2015.01.006

Cited by 36 publications

(48 citation statements)

References 41 publications

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“…Furthermore, we confirmed findings from previous works showing that AD is associated with the long CR1 isoform [35,36], and that low CR1 density could explain the association between CR1 and AD [20], as identified by GWAS [3]. …”

Section: Discussionsupporting

confidence: 91%

“…With regards to the CR1 length polymorphism, our results generally followed the same trends as those observed in our previous work [20]. No association between length polymorphism-associated genotype and density polymorphism-associated genotype was observed.…”

Section: Discussionsupporting

confidence: 89%

“…Moreover, the anti-CR1 moAb J3B11, and the TO5 and E11 moAbs were also used in flow cytometry or in control experiments [20]. A standard curve was obtained from donors of known CR1 antigenic sites, with a density ranging from 180 to 1000 sites per erythrocyte.…”

Section: Methodsmentioning

confidence: 99%

“…In Caucasians, erythrocytes from different healthy subjects show up to a 10-fold variation in the number of CR1 molecules per erythrocyte (range: 150–1200 molecules/erythrocyte) [18]. Moreover, previously published data showed that CR1 density was not correlated with age [19,20]. CR1 density on erythrocytes is genetically associated with an autosomal co-dominant bi-allelic system on the CR1 gene, which is correlated with a Hin dIII restriction fragment length polymorphism (RFLP) [21].…”

Section: Introductionmentioning

confidence: 99%

“…Previous studies showed that the AD risk associated with CR1 can be explained by low density [20] of the long CR1 isoform, CR1*2 (S) [35,36,37]. However, the mechanisms underlying the decrease in CR1 density in AD remain to be elucidated.…”

Section: Introductionmentioning

confidence: 99%

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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

Mahmoudi

Feldman

Kisserli

et al. 2018

IJMS

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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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Section: Discussionsupporting

confidence: 91%

Section: Discussionsupporting

confidence: 89%

Section: Methodsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 3 more Smart Citations

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

Mahmoudi

Feldman

Kisserli

et al. 2018

IJMS

Self Cite

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Complement dysregulation and Alzheimer's disease in Down syndrome

Veteleanu

Pape

Davies

et al. 2022

Alzheimer's & Dementia

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Introduction: Down syndrome (DS) is associated with immune dysregulation and a high risk of early onset Alzheimer's disease (AD). Complement is a key part of innate immunity and driver of pathological inflammation, including neuroinflammation in AD. Complement dysregulation has been reported in DS; however, the pattern of dysregulation and its relationship to AD risk is unclear.Methods: Plasma levels of 14 complement biomarkers were measured in 71 adults with DS and 46 controls to identify DS-associated dysregulation; impact of apolipoprotein E (APOE) ε4 genotype, single nucleotide polymorphisms (SNPs) in CLU and CR1, and dementia on complement biomarkers was assessed.Results: Plasma levels of complement activation products (TCC, iC3b), proteins (C1q, C3, C9), and regulators (C1 inhibitor, factor H, FHR4, clusterin) were significantly elevated in DS versus controls while FI and sCR1 were significantly lower. In DS with AD (n = 13), C3 and FI were significantly decreased compared to non-AD DS (n = 58). Neither APOE genotype nor CLU SNPs impacted complement levels, while rs6656401 in CR1 significantly impacted plasma sCR1 levels. Conclusions:Complement is dysregulated in DS, likely reflecting the generalized immune dysregulation state; measurement may help identify inflammatory events in individuals with DS. Complement biomarkers differed in DS with and without AD and may aid diagnosis and/or prediction.

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