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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 ? (A?) metabolism of AD human is still unclear. Hence, the aim of this study was to investigate genetic influences of CR1 gene on A? 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 A? metabolism, the PLINK software was used to conduct the quality control procedures to enroll appropriate SNPs. Moreover, the correlation between CR1 genotypes and A? 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 A? accumulation in brain. In further analyses, rs17259045 was found to decrease A? accumulation among AD patients. Additionally, our study revealed the genetic variants in rs12567945 could increase CSF A?42 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 A? accumulation. These findings will provide a new basis for the diagnosis and treatment AD.

SUBMITTER: Zhu XC

PROVIDER: S-EPMC7488421 | biostudies-literature | 2020 Sep

REPOSITORIES: biostudies-literature

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

Zhu Xi-Chen XC Dai Wen-Zhuo WZ Ma Tao T

BMC medical genetics 20200912 1

<h4>Background</h4>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.<h4>Methods</h4>All data of AD patients and normal controls (NC) were obtained from alzheimer's disease neu ...[more]

PMID: 32919460

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Project description:Widespread implementation of cerebrospinal fluid (CSF) biomarkers of Alzheimer's disease (AD) in clinical settings requires improved accuracy for diagnosis of prodromal disease and for distinguishing AD from non-AD dementias. Novel and promising CSF biomarkers include neurogranin, a marker of synaptic degeneration, and YKL-40, a marker of neuroinflammation.CSF neurogranin and YKL-40 were measured in a cohort of 338 individuals including cognitively healthy controls and patients with stable mild cognitive impairment (sMCI), MCI who later developed AD (MCI-AD), AD dementia, Parkinson's disease dementia (PDD), dementia with Lewy bodies (DLB), vascular dementia (VaD), and frontotemporal dementia (FTD). The diagnostic accuracy of neurogranin and YKL-40 were compared with the core AD biomarkers, β-amyloid (Aβ42 and Aβ40) and tau.Neurogranin levels were increased in AD and decreased in non-AD dementia compared with healthy controls. As a result, AD patients showed considerably higher CSF levels of neurogranin than DLB/PDD, VaD and FTD patients. CSF YKL-40 levels were increased in AD compared with DLB/PDD but not with VaD or FTD. Neither CSF neurogranin nor YKL-40 levels differed significantly between sMCI patients and MCI-AD patients. Both biomarkers correlated positively with CSF Aβ40 and tau. CSF neurogranin and YKL-40 could separate AD dementia from non-AD dementias (neurogranin, area under the curve [AUC] = 0.761; YKL-40, AUC = 0.604; Aβ42/neurogranin, AUC = 0.849; Aβ42/YKL-40, AUC = 0.785), but the diagnostic accuracy was not better compared to CSF Aβ and tau (Aβ42, AUC = 0.755; tau AUC = 0.858; Aβ42/tau, AUC = 0.895; Aβ42/Aβ40, AUC = 0.881). Similar results were obtained when separating sMCI from MCI-AD cases.CSF neurogranin and YKL-40 do not improve the diagnostic accuracy of either prodromal AD or AD dementia when compared to the core CSF AD biomarkers. Nevertheless, the CSF level of neurogranin is selectively increased in AD dementia, whereas YKL-40 is increased in both AD and FTD suggesting that synaptic degeneration and glial activation may be important in these neurodegenerative conditions.

Dataset Information

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

Publications

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

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