Updated Meta-Analysis of BIN1, CR1, MS4A6A, CLU, and ABCA7 Variants in Alzheimer’s Disease

Almeida, Jucimara Ferreira Figueiredo; Santos, Lígia Ramos dos; Trancozo, Maíra; Paula, Fabiana Martins de

doi:10.1007/s12031-018-1045-y

Cited by 40 publications

(26 citation statements)

References 41 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The different SNPs on the BIN1 gene may be in disequilibrium and may add independently from each other to the risk of AD 14 . Here, we focused on rs744373 because this SNP is most frequently reported to be associated with AD across different GWAS studies 3,7 (see also AlzGene database at http://www.alzgene.org/) 50 . Although rs744373 is the primary BIN1 SNP associated with increased AD risk, a previous study suggested that the Indel rs59335482 is associated with increased BIN1 mRNA in post-mortem analyzed brains from AD patients, suggesting that rs59335482 is the functionally effective BIN1 genetic variant associated with AD risk.…”

Section: Discussionmentioning

confidence: 99%

“…While late onset AD is an age-related disease, results from twin and family studies have emphasized that ~50% of phenotypic variance in AD can be explained by genetic variations 2 . Recent genome-wide association studies (GWAS) have identified several loci that are associated with increased risk of AD, among which the single nucleotide polymorphisms (SNPs) in the bridging integrator 1 ( BIN1 ) gene show the second highest odds-ratios for sporadic AD, superseded only by apolipoprotein E ( APOE ) variants 3–7 . Specifically, the most frequently reported BIN1 AD risk variant is the SNP rs744373 which shows a global allele frequency of 37% and is associated with an increase in AD risk by an odds-ratio of 1.17–1.19 5,7–10 .…”

Section: Introductionmentioning

confidence: 99%

“…Recent genome-wide association studies (GWAS) have identified several loci that are associated with increased risk of AD, among which the single nucleotide polymorphisms (SNPs) in the bridging integrator 1 ( BIN1 ) gene show the second highest odds-ratios for sporadic AD, superseded only by apolipoprotein E ( APOE ) variants 3–7 . Specifically, the most frequently reported BIN1 AD risk variant is the SNP rs744373 which shows a global allele frequency of 37% and is associated with an increase in AD risk by an odds-ratio of 1.17–1.19 5,7–10 . Thus, understanding the mechanisms by which BIN1 and in particular the rs744373 SNP contributes to AD risk will lead to a better understanding of the pathomechanisms of AD and help uncover novel therapeutic targets.…”

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

The BIN1 rs744373 SNP is associated with increased tau-PET levels and impaired memory

et al. 2019

View full text Add to dashboard Cite

The single nucleotide polymorphism (SNP) rs744373 in the bridging integrator-1 gene (BIN1) is a risk factor for Alzheimer’s disease (AD). In the brain, BIN1 is involved in endocytosis and sustaining cytoskeleton integrity. Post-mortem and in vitro studies suggest that BIN1-associated AD risk is mediated by increased tau pathology but whether rs744373 is associated with increased tau pathology in vivo is unknown. Here we find in 89 older individuals without dementia, that BIN1 rs744373 risk-allele carriers show higher AV1451 tau-PET across brain regions corresponding to Braak stages II–VI. In contrast, the BIN1 rs744373 SNP was not associated with AV45 amyloid-PET uptake. Furthermore, the rs744373 risk-allele was associated with worse memory performance, mediated by increased global tau levels. Together, our findings suggest that the BIN1 rs744373 SNP is associated with increased tau but not beta-amyloid pathology, suggesting that alterations in BIN1 may contribute to memory deficits via increased tau pathology.

show abstract

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

The BIN1 rs744373 SNP is associated with increased tau-PET levels and impaired memory

et al. 2019

View full text Add to dashboard Cite

show abstract

“…Other meta-analyses have then confirmed the genetic involvement of ABCA7 with the disease (Almeida, dos Santos, Trancozo, & de Paula, 2018;Ma et al, 2018). To date, the risky G allele of the rs3764650 has been associated with reduced ABCA7 expression, hippocampal atrophy, increased plaque pathology and subsequent cognitive decline (Andrews, Das, Cherbuin, Anstey, & Easteal, 2016;Ma et al, 2018;Ramirez et al, 2016;Shulman et al, 2013;Vasquez, Fardo, & Estus, 2013), whereas the G1527A mutation affected Aβ deposition (Hughes et al, 2014).…”

Section: Abca1 and Abca7mentioning

confidence: 91%

High‐density lipoprotein‐related cholesterol metabolism in Alzheimer’s disease

Pedrini

Chatterjee

Hone

et al. 2020

Journal of Neurochemistry

View full text Add to dashboard Cite

Alzheimer's disease (AD) is the leading cause of dementia in the elderly and the number of affected individuals is set to increase in the next decades. The two main features of AD are represented by extracellular amyloid plaques of amyloid β (Aβ) in the brain parenchyma and intracellular neurofibrillary tangles of tau protein. In the past decades several lines of evidence have indicated that high-density lipoproteins (HDL) are strongly involved in the aetiology and the progression of the disease, although the overall analysis of HDL levels and their association with cognitive functions somehow lacked consensus. Many of the proteins associated with HDL are also linked to AD and Aβ formation/catabolism, some displaying protective features while others do not, it is not surprising the association between HDL levels and AD provided confounding results. It is therefore possible that components of HDL 'protein cargo', more than the HDL levels alone, are responsible for neuroprotection and affect Aβ formation and/or deposition.

show abstract

“…However, in spite of the progress in understanding risk factors related to AD development, the underlying mechanisms involved in this disease have not been completely understood till now, and to date there is no curative treatment for AD [5,6]. Now many genes are proved to significantly influence AD risk, among which the complement component (3b/4b) receptor 1 gene (CR1) has been proved to affect AD susceptibility across different ethnic and districts groups [7][8][9][10][11][12]. Currently, CR1 has been postulated to be a key factor for AD pathogenesis because of its role in regulating complement activity by acting as a receptor of complement C3b protein [13].…”

Section: Introductionmentioning

confidence: 99%

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

Zhu

Dai

2020

BMC Med Genet

View full text Add to dashboard Cite

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.

show abstract

Updated Meta-Analysis of BIN1, CR1, MS4A6A, CLU, and ABCA7 Variants in Alzheimer’s Disease

Cited by 40 publications

References 41 publications

The BIN1 rs744373 SNP is associated with increased tau-PET levels and impaired memory

The BIN1 rs744373 SNP is associated with increased tau-PET levels and impaired memory

High‐density lipoprotein‐related cholesterol metabolism in Alzheimer’s disease

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

Contact Info

Product

Resources

About