免疫基因变异：与认知及阿尔茨海默病病理学的关系
Immunity gene variant: Relation to cognition and Alzheimer's disease pathology.
作者信息
Pyun Jung-Min, Park Young Ho, Hodges Angela, Jang Jae-Won, Bice Paula J, Kim SangYun, Saykin Andrew J, Nho Kwangsik
机构信息
Department of Neurology Seoul National University Bundang Hospital and Seoul National University College of Medicine Seongnam Republic of Korea.
Department of Neurology Soonchunhyang University Seoul Hospital Soonchunhyang University College of Medicine Seoul Republic of Korea.
出版信息
Alzheimers Dement (Amst). 2022 Jun 21;14(1):e12317. doi: 10.1002/dad2.12317. eCollection 2022.
INTRODUCTION
We investigated single-nucleotide polymorphisms (SNPs) in , an innate immunity gene and modulator of amyloid beta in Alzheimer's disease (AD), for association with cognition and AD biomarkers.
METHODS
We used data from the Alzheimer's Disease Neuroimaging Initiative (ADNI; = 1565) and AddNeuroMed ( = 633) as discovery and replication samples, respectively. We performed gene-based association analysis of SNPs in with cognitive performance and SNP-based association analysis with cognitive decline and amyloid, tau, and neurodegeneration biomarkers for AD.
RESULTS
Gene-based association analysis showed that was significantly associated with cognitive performance. Particularly, rs10751647 in was associated with less cognitive decline, less amyloid and tau burden, and less brain atrophy in ADNI. The association of rs10751647 with cognitive decline and brain atrophy was replicated in AddNeuroMed.
DISCUSSION
This suggests that rs10751647 in is associated with less vulnerability for cognitive decline and AD biomarkers, providing mechanistic insight regarding involvement of immunity and infection in AD.
HIGHLIGHTS
is significantly associated with cognitive performance.rs10751647 in is associated with cognitive decline rates with replication.rs10751647 is associated with amyloid beta load, cerebrospinal fluid phosphorylated tau levels, and brain atrophy.rs10751647 is associated with expression levels in blood and brain.rs10751647 in is related to less vulnerability to Alzheimer's disease pathogenesis.
引言
我们研究了一种先天性免疫基因以及阿尔茨海默病（AD）中β淀粉样蛋白调节剂中的单核苷酸多态性（SNP），以探讨其与认知及AD生物标志物之间的关联。
方法
我们分别使用来自阿尔茨海默病神经影像学倡议（ADNI；n = 1565）和AddNeuroMed（n = 633）的数据作为发现样本和重复样本。我们对该基因中的SNP进行了基于基因的与认知表现的关联分析，以及基于SNP的与AD的认知衰退、淀粉样蛋白、tau蛋白和神经退行性变生物标志物的关联分析。
结果
基于基因的关联分析表明，该基因与认知表现显著相关。特别是，该基因中的rs10751647与ADNI中较少的认知衰退、较少的淀粉样蛋白和tau蛋白负担以及较少的脑萎缩相关。rs10751647与认知衰退和脑萎缩的关联在AddNeuroMed中得到了重复验证。
讨论
这表明该基因中的rs10751647与认知衰退和AD生物标志物的易感性较低相关，为免疫和感染在AD中的作用机制提供了见解。
要点
该基因与认知表现显著相关。该基因中的rs10751647与认知衰退率相关且得到重复验证。rs10751647与β淀粉样蛋白负荷、脑脊液磷酸化tau蛋白水平和脑萎缩相关。rs10751647与血液和大脑中的该基因表达水平相关。该基因中的rs10751647与阿尔茨海默病发病机制的易感性较低相关。
Zotero 插件