A Pathway-Specific Polygenic Risk Score Is Associated with Tau Pathology and Cognitive Decline | |
Sun, Yuqing1,2,3; Wang, Meng1,2,3; Zhao, Yuxin1,2,3; Hu, Ke1,2,3; Liu, Yong4; Liu, Bing5,6 | |
发表期刊 | JOURNAL OF ALZHEIMERS DISEASE |
ISSN | 1387-2877 |
2022 | |
卷号 | 85期号:4页码:1745-1754 |
摘要 | Background: Tauopathy is a primary neuropathological hallmark of Alzheimer's disease with a strong relationship to cognitive impairment. In the brain, tau aggregation is associated with the regulation of tau kinases and the binding ability of tau to microtubules. Objective: To explore the potential for using specific polygenic risk scores (PRSs), combining the genetic influences involved in tau-protein kinases and the tau-protein binding pathway, as predictors of tau pathology and cognitive decline in non-demented individuals. Methods: We computed a pathway-specific PRS using summary statistics from previous large-scale genome-wide association studies of dementia. We examined whether PRS is related to tau uptake in positron emission tomography (PET), tau levels, and the rate of tau level changes in cerebrospinal fluid (CSF). We further assessed whether PRS is associated with memory impairment mediated by CSF tau levels. Results: A higher PRS was related to elevated CSF tau levels and tau-PET uptake at baseline, as well as greater rates of change in CSF tau levels. Moreover, PRS was associated with memory impairment, mediated by increased CSF tau levels. The association between PRS and tau pathology was significant when APOE was excluded, even among females. However, the effect of PRS on cognitive decline appeared to be driven by the inclusion of APOE. Conclusion: The influence of genetic risk in a specific tau-related biological pathway may make an individual more susceptible to tau pathology, resulting in cognitive dysfunction in an early preclinical phase of the disease. |
关键词 | Alzheimer's disease cognitive function genetic risk scores pathway tau |
DOI | 10.3233/JAD-215163 |
关键词[WOS] | ALZHEIMERS-DISEASE ; CEREBROSPINAL-FLUID ; NEUROFIBRILLARY TANGLES ; BIOMARKERS ; PHOSPHORYLATION ; PROTEIN ; ONSET ; AGE |
收录类别 | SCI |
语种 | 英语 |
资助项目 | National Natural Science Foundation of China[81771451] ; National Natural Science Foundation of China[81871438] ; Beijing Natural Science Funds for Distinguished Young Scholar[JQ20036] ; Alzheimer's Disease Neuroimaging Initiative (ADNI) (National Institutes of Health)[U01AG024904] ; DOD ADNI (Department of Defense)[W81XWH-12-2-0012] ; National Institute on Aging ; National Institute of Biomedical Imaging and Bioengineering ; Alzheimer's Association ; Alzheimer's Drug Discovery Foundation ; Araclon Biotech ; Biogen ; CereSpir, Inc. ; Cogstate ; Elan Pharmaceuticals, Inc. ; Eli Lilly and Company ; EuroImmun ; F. Hoffmann-La Roche Ltd, ; Genentech, Inc. ; Fujirebio ; GE Healthcare ; IXICO Ltd. ; Janssen Alzheimer Immunotherapy Research & Development, LLC. ; Johnson & Johnson Pharmaceutical Research & Development LLC. ; Lumosity ; Lundbeck ; Merck Co., Inc. ; Meso Scale Diagnostics, LLC. ; NeuroRx Research ; Neurotrack Technologies ; Novartis Pharmaceuticals Corporation ; Pfizer Inc. ; Piramal Imaging ; Servier ; Takeda Pharmaceutical Company ; Transition Therapeutics ; Canadian Institutes of Health Research ; AbbVie ; Bristol-Myers Squibb Company ; Eisai Inc. |
项目资助者 | National Natural Science Foundation of China ; Beijing Natural Science Funds for Distinguished Young Scholar ; Alzheimer's Disease Neuroimaging Initiative (ADNI) (National Institutes of Health) ; DOD ADNI (Department of Defense) ; National Institute on Aging ; National Institute of Biomedical Imaging and Bioengineering ; Alzheimer's Association ; Alzheimer's Drug Discovery Foundation ; Araclon Biotech ; Biogen ; CereSpir, Inc. ; Cogstate ; Elan Pharmaceuticals, Inc. ; Eli Lilly and Company ; EuroImmun ; F. Hoffmann-La Roche Ltd, ; Genentech, Inc. ; Fujirebio ; GE Healthcare ; IXICO Ltd. ; Janssen Alzheimer Immunotherapy Research & Development, LLC. ; Johnson & Johnson Pharmaceutical Research & Development LLC. ; Lumosity ; Lundbeck ; Merck Co., Inc. ; Meso Scale Diagnostics, LLC. ; NeuroRx Research ; Neurotrack Technologies ; Novartis Pharmaceuticals Corporation ; Pfizer Inc. ; Piramal Imaging ; Servier ; Takeda Pharmaceutical Company ; Transition Therapeutics ; Canadian Institutes of Health Research ; AbbVie ; Bristol-Myers Squibb Company ; Eisai Inc. |
WOS研究方向 | Neurosciences & Neurology |
WOS类目 | Neurosciences |
WOS记录号 | WOS:000759157200028 |
出版者 | IOS PRESS |
七大方向——子方向分类 | 医学影像处理与分析 |
引用统计 | |
文献类型 | 期刊论文 |
条目标识符 | http://ir.ia.ac.cn/handle/173211/48067 |
专题 | 脑图谱与类脑智能实验室_脑网络组研究 |
通讯作者 | Liu, Yong; Liu, Bing |
作者单位 | 1.Univ Chinese Acad Sci, Sch Artificial Intelligence, Beijing, Peoples R China 2.Chinese Acad Sci, Brainnetome Ctr, Inst Automat, Beijing, Peoples R China 3.Chinese Acad Sci, Natl Lab Pattern Recognit, Inst Automat, Beijing, Peoples R China 4.Beijing Univ Posts & Telecommun, Sch Artificial Intelligence, Beijing 100876, Peoples R China 5.Beijing Normal Univ, State Key Lab Cognit Neurosci & Learning, Beijing 100875, Peoples R China 6.Chinese Inst Brain Res, Beijing, Peoples R China |
第一作者单位 | 模式识别国家重点实验室 |
推荐引用方式 GB/T 7714 | Sun, Yuqing,Wang, Meng,Zhao, Yuxin,et al. A Pathway-Specific Polygenic Risk Score Is Associated with Tau Pathology and Cognitive Decline[J]. JOURNAL OF ALZHEIMERS DISEASE,2022,85(4):1745-1754. |
APA | Sun, Yuqing,Wang, Meng,Zhao, Yuxin,Hu, Ke,Liu, Yong,&Liu, Bing.(2022).A Pathway-Specific Polygenic Risk Score Is Associated with Tau Pathology and Cognitive Decline.JOURNAL OF ALZHEIMERS DISEASE,85(4),1745-1754. |
MLA | Sun, Yuqing,et al."A Pathway-Specific Polygenic Risk Score Is Associated with Tau Pathology and Cognitive Decline".JOURNAL OF ALZHEIMERS DISEASE 85.4(2022):1745-1754. |
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