Endophenotype-based in silico network medicine discovery combined with insurance record data mining identifies sildenafil as a candidate drug for Alzheimer's disease.
Endophenotype-based in silico network medicine discovery combined with insurance record data mining identifies sildenafil as a candidate drug for Alzheimer's disease.
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基于内表型的计算机网络医学发现结合保险记录数据挖掘将西地那非确定为阿尔茨海默病的候选药物。
DOI：
10.1038/s43587-021-00138-z
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发表时间：
2021-12
期刊：
影响因子：
--
通讯作者：
Cheng, Feixiong
中科院分区：
文献类型：
--
作者：
Fang, Jiansong;Zhang, Pengyue;Zhou, Yadi;Chiang, Chien-Wei;Tan, Juan;Hou, Yuan;Stauffer, Shaun;Li, Lang;Pieper, Andrew A.;Cummings, Jeffrey;Cheng, Feixiong
We developed an endophenotype disease module-based methodology for Alzheimer’s disease (AD) drug repurposing and identified sildenafil as a potential disease risk modifier. Based on retrospective case-control pharmacoepidemiologic analyses of insurance claims data for 7.23 million individuals, we found that sildenafil usage was significantly associated with a 69% reduced risk of AD (hazard ratio = 0.31, 95% confidence interval 0.25–0.39, P<1.0×10−8). Propensity score stratified analyses confirmed that sildenafil is significantly associated with a decreased risk of AD across all four drug cohorts we tested (diltiazem, glimepiride, losartan and metformin) after adjusting age, sex, race, and disease comorbidities. We also found that sildenafil increases neurite growth and decreases phospho-tau expression in AD patient-induced pluripotent stem cells-derived neuron models, supporting mechanistically its potential beneficial effect in Alzheimer’s disease. The association between sildenafil use and decreased incidence of AD does not establish causality or its direction, which requires a randomized clinical trial approach.
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DOI：
10.1016/j.jalz.2017.11.006
发表时间：
2018-05
期刊：
Alzheimer's & dementia : the journal of the Alzheimer's Association
影响因子：
--
作者：
Chung J;Wang X;Maruyama T;Ma Y;Zhang X;Mez J;Sherva R;Takeyama H;Alzheimer's Disease Neuroimaging Initiative;Lunetta KL;Farrer LA;Jun GR
通讯作者：
Jun GR
影响因子：
16.6
作者：
Cheng F;Desai RJ;Handy DE;Wang R;Schneeweiss S;Barabási AL;Loscalzo J
通讯作者：
Loscalzo J
DOI：
10.1002/wsbm.1417
发表时间：
2018-07
期刊：
Wiley interdisciplinary reviews. Systems biology and medicine
影响因子：
--
作者：
Barbarino JM;Whirl-Carrillo M;Altman RB;Klein TE
通讯作者：
Klein TE
DOI：
10.1186/s13195-017-0262-x
发表时间：
2017-05-31
期刊：
Alzheimer's research & therapy
影响因子：
--
作者：
Gabin JM;Tambs K;Saltvedt I;Sund E;Holmen J
通讯作者：
Holmen J
影响因子：
14.9
作者：
Gaulton A;Hersey A;Nowotka M;Bento AP;Chambers J;Mendez D;Mutowo P;Atkinson F;Bellis LJ;Cibrián-Uhalte E;Davies M;Dedman N;Karlsson A;Magariños MP;Overington JP;Papadatos G;Smit I;Leach AR
通讯作者：
Leach AR