期刊
JOURNAL OF HUMAN GENETICS
卷 67, 期 8, 页码 459-463出版社
SPRINGERNATURE
DOI: 10.1038/s10038-022-01026-z
关键词
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资金
- National Natural Science Foundation of China [82071201, 81971032]
- National Key R&D Programof China [2018YFC1314700]
- Research Start-up Fund of Huashan Hospital, Fudan University [2022QD002]
- Research Start-up Fund of Huashan Hospital [2022QD002]
- Excellence 2025 Talent Cultivation Program [3030277001]
- Shanghai Municipal Science and Technology Major Project [2018SHZDZX01]
- ZHANGJIANG LAB
- Tianqiao and Chrissy Chen Institute
- State Key Laboratory of Neurobiology and Frontiers Center for Brain Science of Ministry of Education, Fudan University
- ADNI (National Institutes of Health) [U01 AG024904]
- DOD ADNI (Department of Defense) [W81XWH-12-20012]
- National Institute on Aging
- National Institute of Biomedical Imaging and Bioengineering
- Canadian Institutes of Health Research
This study identified a significant SNP, particularly rs769449 in the APOE gene, associated with plasma p-tau181 levels. The findings suggest that plasma p-tau181 levels have the potential to identify risk for AD in elderly individuals, and the variation in the APOE gene may be involved in the regulation of plasma p-tau181 levels.
As a promising diagnostic and prognostic biomarker for Alzheimer's Disease (AD), plasma p-tau181 is robustly differentiated AD dementia from non-AD neurodegenerative diseases. We aimed to discover single nucleotide polymorphisms (SNPs) associated with plasma phosphorylated tau at threonine 181 (p-tau181) levels that affect the risk of developing AD. We carried out a genome-wide association study for plasma p-tau181 levels using participants from the Alzheimer's Disease Neuroimaging Initiative (ADNI). The thresholds of P < 5 x 10(-6) was used for suggestive associations, and thresholds of P < 5 x 10(-8) was used for significant associations. Subsequently, we tested whether the associations remained significant in subgroup analysis and examined the impact of SNPs on the longitudinal changes in plasma p-tau181 levels. A total of 714 eligible non-Hispanic white participants with plasma p-tau181 data were included. The most significant SNP (rs769449, P = 6.26 x 10(-8)) in APOE gene was suggestively associated with plasma p-tau181, which is close to the genome-wide significance threshold. The minor allele (A) of rs769449 in the APOE was associated with higher plasma p-tau181 levels in a dose-dependent fashion. Besides, rs769449- A carriers were more likely to exhibit a greater longitudinal cognitive decline (P = 0.03). Our results suggest that the AD risk variant in the APOE gene participates in the regulation of plasma p-tau181. The plasma p-tau181 concentration could be a useful endophenotype for identifying risk for AD in elderly individuals.
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