Effect of CR1 Genetic Variants on Cerebrospinal Fluid and Neuroimaging Biomarkers in Healthy, Mild Cognitive Impairment and Alzheimer's Disease Cohorts

被引：18

作者：

Zhu, Xi-Chen ^{[1
]}

Wang, Hui-Fu ^{[1
]}

Jiang, Teng ^{[1
,2
]}

Lu, Huan ^{[1
]}

Tan, Meng-Shan ^{[3
]}

Tan, Chen-Chen ^{[3
]}

Tan, Lin ^{[4
]}

Tan, Lan ^{[1
,3
,4
]}

Yu, Jin-Tai ^{[1
,3
,4
,5
]}

机构：

[1] Nanjing Med Univ, Qingdao Municipal Hosp, Dept Neurol, 5 Donghai Middle Rd, Qingdao 266071, Shandong, Peoples R China

[2] Nanjing Med Univ, Nanjing Hosp 1, Dept Neurol, Nanjing, Jiangsu, Peoples R China

[3] Qingdao Univ, Sch Med, Qingdao Municipal Hosp, Dept Neurol, Qingdao, Peoples R China

[4] Ocean Univ China, Qingdao Municipal Hosp, Dept Neurol, Coll Med & Pharmaceut, Qingdao, Peoples R China

[5] Univ Calif San Francisco, Memory & Aging Ctr, Dept Neurol, 675 Nelson Rising Lane,Suite 190,Box 1207, San Francisco, CA 94158 USA

来源：

MOLECULAR NEUROBIOLOGY | 2017年 / 54卷 / 01期

基金：

中国国家自然科学基金; 加拿大健康研究院; 美国国家卫生研究院;

关键词：

CR1; Alzheimer's disease; Amyloid deposition; Brain structure; CSF; Glucose metabolism; Neuroimaging; GENOME-WIDE ASSOCIATION; MEDIAL TEMPORAL-LOBE; FUNCTIONAL CONNECTIVITY; DIAGNOSTIC GUIDELINES; IDENTIFIES VARIANTS; NATIONAL INSTITUTE; GLUCOSE-METABOLISM; ENTORHINAL CORTEX; COMMON VARIANTS; FLORBETAPIR-PET;

D O I：

10.1007/s12035-015-9638-8

中图分类号：

Q189 [神经科学];

学科分类号：

071006 ;

摘要：

The complement component (3b/4b) receptor 1 gene (CR1) is considered as one of the most important genetic susceptibility loci in Alzheimer's disease (AD). However, to date, few studies were performed to discover the possible effect of CR1 genetic variants on AD pathology in the brain. Here, we evaluated the potential role of CR1 common variants in AD-related pathology by assessing neuroimaging biomarkers and cerebrospinal fluid (CSF) proteins. Finally, a total of 812 subjects from the Alzheimer's disease Neuroimaging Initiative database and eight single nucleotide polymorphisms (SNPs) after quality control procedures are enrolled in our analysis. After applied to multiple linear regression models, significant associations were proved to exist between rs4844609 and amyloid deposition in cingulated, frontal, parietal, and temporal on florbetapir 18F amyloid positron emission tomography. In the analysis of the impacts of CR1 genetic variants on brain structures, three SNPs (rs12034383, rs3737002, and rs6691117) were significantly linked to the changes in volume of middle temporal. In addition, rs10779339 showed a negative connection with the cerebral metabolism rate of glucose in the right temporal on 18F-fluorodeoxyglucose PET imaging. However, no significant statistical findings were detected between CR1 genetic variants and CSF proteins (amyloid beta, total-tau, and p-tau) at baseline diagnose or in the follow-up study of 2 years. The results of our study indicated that CR1 plays a vital role in AD pathology mainly by influencing A beta deposition, brain structure, and glucose metabolism during AD progression.

引用

页码：551 / 562

页数：12

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