期刊
GENES
卷 12, 期 3, 页码 -出版社
MDPI
DOI: 10.3390/genes12030443
关键词
complement; complement receptor 1; clusterin; late-onset Alzheimer’ s disease; genetics; neuroinflammation
资金
- U.K. Dementia Research Institute from U.K. DRI Ltd.
- U.K. Medical Research Council
- Alzheimer's Society
- Alzheimer's Research U.K.
- MRC [UKDRI-3002] Funding Source: UKRI
Late-onset Alzheimer's disease is a neurodegenerative disease with uncertain etiology. Research suggests that complement genes may be associated with the risk of the disease, particularly CLU and CR1 genes, but further studies are needed for confirmation.
Late-onset Alzheimer's disease (LOAD), the most common cause of dementia, and a huge global health challenge, is a neurodegenerative disease of uncertain aetiology. To deliver effective diagnostics and therapeutics, understanding the molecular basis of the disease is essential. Contemporary large genome-wide association studies (GWAS) have identified over seventy novel genetic susceptibility loci for LOAD. Most are implicated in microglial or inflammatory pathways, bringing inflammation to the fore as a candidate pathological pathway. Among the most significant GWAS hits are three complement genes: CLU, encoding the fluid-phase complement inhibitor clusterin; CR1 encoding complement receptor 1 (CR1); and recently, C1S encoding the complement enzyme C1s. Complement activation is a critical driver of inflammation; changes in complement genes may impact risk by altering the inflammatory status in the brain. To assess complement gene association with LOAD risk, we manually created a comprehensive complement gene list and tested these in gene-set analysis with LOAD summary statistics. We confirmed associations of CLU and CR1 genes with LOAD but showed no significant associations for the complement gene-set when excluding CLU and CR1. No significant association with other complement genes, including C1S, was seen in the IGAP dataset; however, these may emerge from larger datasets.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据