Impacts of CR1 genetic variants on cerebrospinal fluid and neuroimaging biomarkers in alzheimer’s disease

Abstract

Background The complement component (3b/4b) receptor 1 gene (CR1) gene has been proved to affect the susceptibility of Alzheimer’s disease (AD) in different ethnic and districts groups. However, the effect of CR1 genetic variants on amyloid β (Aβ) metabolism of AD human is still unclear. Hence, the aim of this study was to investigate genetic influences of CR1 gene on Aβ metabolism. Methods All data of AD patients and normal controls (NC) were obtained from alzheimer’s disease neuroimaging initiative database (ADNI) database. In order to assess the effect of each single nucleotide polymorphism (SNP) of CR1 on Aβ metabolism, the PLINK software was used to conduct the quality control procedures to enroll appropriate SNPs. Moreover, the correlation between CR1 genotypes and Aβ metabolism in all participants were estimated with multiple linear regression models. Results After quality control procedures, a total of 329 samples and 83 SNPs were enrolled in our study. Moreover, our results identified five SNPs (rs10494884, rs11118322, rs1323721, rs17259045 and rs41308433), which were linked to Aβ accumulation in brain. In further analyses, rs17259045 was found to decrease Aβ accumulation among AD patients. Additionally, our study revealed the genetic variants in rs12567945 could increase CSF Aβ42 in NC population. Conclusions Our study had revealed several novel SNPs in CR1 genes which might be involved in the progression of AD via regulating Aβ accumulation. These findings will provide a new basis for the diagnosis and treatment AD.

Microglia in Alzheimer’s Disease: A Target for Therapeutic Intervention

“…In addition to APOE , CR1 is also an important genetic susceptibility locus for LOAD. There is growing evidence that some single-nucleotide polymorphisms (SNPs) of CR1 confer AD risk and are associated with Aβ accumulation (Lambert et al, 2009 ; Zhu et al, 2015 , 2020 ). The potential role of CR1 in AD pathogenesis may be related to microglia-mediated Aβ phagocytosis.…”

Explore the role of CR1 genetic variants in late-onset Alzheimer’s disease susceptibility

“…Moreover, CR1 has a close connection with amyloid plaque burden during aging (Chibnik et al, 2011;Gandy et al, 2013;Thambisetty et al, 2013). In addition, CR1 genetic variants are proved to influence intelligence for modulating Aβ in brain (Chibnik et al, 2011;Zhu et al, 2020) and CSF (Zhu et al, 2017;Zhu et al, 2020). Hence, it is reasonable to draw the conclusions that CR1 polymorphisms take part in the pathogenesis and development of LOAD.…”

“…Importantly, CR1 is a necessary component of complement system. In addition, CR1 is reported to participate in the clearance of Aβ in two pathways, peripherally by erythrocyte and directly in the brain (Rogers et al , 1992; Ghiso et al , 2004; Rogers et al , 2006; Zhu et al , 2015; Zhu et al , 2020). Moreover, CR1 has a close connection with amyloid plaque burden during aging (Chibnik et al , 2011; Gandy et al , 2013; Thambisetty et al , 2013).…”

“…Besides the APOE gene, many genes have been identified their relation to LOAD risk, such as Clusterin (Carrasquillo et al, 2010;Zhang et al, 2015), PICALM (Carrasquillo et al, 2010;Zhang et al, 2015), the complement component (3b/4b) receptor 1 (CR1) (Carrasquillo et al, 2010), EPHA1 (Naj et al, 2011) and CD33 (Hollingworth et al, 2011;Naj et al, 2011). CR1 gene is reported as one important genetic susceptibility locus in LOAD according to recent studies (Kucukkilic et al, 2018;Kretzschmar et al, 2020;Zhu et al, 2020). CR1, also known as CD35, lies in chromosome 1 at the locus 1q32 in a genetic cluster of complement-related genes.…”

Association Between Common Variants of APOE, ABCA7, A2M, BACE1, and Cerebrospinal Fluid Biomarkers in Alzheimer’s Disease: Data from the PUMCH Dementia Cohort

“…With the Alzheimer's Disease Neuroimaging Initiative (ADNI) database, previous studies have investigated the correlation between 15 ABCA7 and 83 CR1 SNPs and CSF biomarkers. However, most of the SNPs are in the non-coding regions, such as intron and untranslated region [12,13]. Fewer studies target the variants located in the coding regions.…”