Predictive metabolic networks reveal sex- and APOE genotype-specific metabolic signatures and drivers for precision medicine in Alzheimer's disease.
Predictive metabolic networks reveal sex- and APOE genotype-specific metabolic signatures and drivers for precision medicine in Alzheimer's disease.
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DOI：
10.1002/alz.12675
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发表时间：
2023-02
影响因子：
14
通讯作者：
Kaddurah-Daouk, Rima
中科院分区：
文献类型：
--
作者：
Chang, Rui;Trushina, Eugenia;Zhu, Kuixi;Zaidi, Syed Shujaat Ali;Lau, Branden M.;Kueider-Paisley, Alexandra;Moein, Sara;He, Qianying;Alamprese, Melissa L.;Vagnerova, Barbora;Tang, Andrew;Vijayan, Ramachandran;Liu, Yanyun;Saykin, Andrew J.;Brinton, Roberta D.;Kaddurah-Daouk, Rima
关键词：
LOAD是一种复杂的神经退行性疾病，以多个进展期、糖代谢紊乱、AD病理和不可避免的认知功能下降为特征。发现性别、载脂蛋白E基因和疾病进展阶段特有的代谢特征可以为个性化负荷药物提供关键的见解。根据ADNI队列中656份血清样本中127种代谢物的变化，构建了性别和载脂蛋白E特异性代谢网络。应用先进的分析平台识别与性别和/或载脂蛋白ɛ4聚集的代谢驱动因素和签名，建立与认知功能显著相关的预测疾病状态的患者特定生物标记物。载脂蛋白Eɛ4的存在将代谢特征转变为以磷脂酰胆碱为重点的特征，覆盖了AD患者血清代谢物的性别差异。这些发现为开发个性化医学诊断平台提供了初步但关键的一步，通过整合代谢组学和认知评估，通过计算网络建模为AD患者亚组确定有针对性的精确治疗方法。
LOAD is a complex neurodegenerative disease characterized by multiple progressive stages, glucose metabolic dysregulation, AD pathology, and inexorable cognitive decline. Discovery of metabolic profiles unique to sex, APOE-genotype and stage of disease progression could provide critical insights for personalized LOAD medicine. Sex- and APOE-specific metabolic networks were constructed based on changes in 127 metabolites of 656 serum samples from the ADNI cohort. Application of advanced analytical platform identified metabolic drivers and signatures clustered with sex and/or APOEɛ4, establishing patient-specific biomarkers predictive of disease state that significantly associated with cognitive function. Presence of the APOEɛ4 shifts metabolic signatures to a phosphatidylcholine-focused profile overriding sex-specific differences in serum metabolites of AD patients. These findings provide an initial but critical step in developing a diagnostic platform for personalized medicine by integrating metabolomic profiling and cognitive assessments to identify targeted precision therapeutics for AD patient subgroups through computational network modeling.
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影响因子：
64.8
作者：
Hur JY;Frost GR;Wu X;Crump C;Pan SJ;Wong E;Barros M;Li T;Nie P;Zhai Y;Wang JC;Tcw J;Guo L;McKenzie A;Ming C;Zhou X;Wang M;Sagi Y;Renton AE;Esposito BT;Kim Y;Sadleir KR;Trinh I;Rissman RA;Vassar R;Zhang B;Johnson DS;Masliah E;Greengard P;Goate A;Li YM
通讯作者：
Li YM
影响因子：
14
作者：
Horgusluoglu, Emrin;Neff, Ryan;Song, Won-Min;Wang, Minghui;Wang, Qian;Arnold, Matthias;Krumsiek, Jan;Galindo-Prieto, Beatriz;Ming, Chen;Nho, Kwangsik;Kastenmueller, Gabi;Han, Xianlin;Baillie, Rebecca;Zeng, Qi;Andrews, Shea;Cheng, Haoxiang;Hao, Ke;Goate, Alison;Bennett, David A.;Saykin, Andrew J.;Kaddurah-Daouk, Rima;Zhang, Bin
通讯作者：
Zhang, Bin
DOI：
10.1016/j.jalz.2010.06.001
发表时间：
2011-05
期刊：
Alzheimer's & dementia : the journal of the Alzheimer's Association
影响因子：
--
作者：
Kaddurah-Daouk R;Rozen S;Matson W;Han X;Hulette CM;Burke JR;Doraiswamy PM;Welsh-Bohmer KA
通讯作者：
Welsh-Bohmer KA
DOI：
10.1016/j.molbrainres.2003.08.004
发表时间：
2003-10-21
期刊：
MOLECULAR BRAIN RESEARCH
影响因子：
--
作者：
Guidetti, P;Schwarcz, R
通讯作者：
Schwarcz, R
DOI：
10.1016/j.xcrm.2020.100138
发表时间：
2020-11-17
期刊：
Cell reports. Medicine
影响因子：
--
作者：
Baloni P;Funk CC;Yan J;Yurkovich JT;Kueider-Paisley A;Nho K;Heinken A;Jia W;Mahmoudiandehkordi S;Louie G;Saykin AJ;Arnold M;Kastenmüller G;Griffiths WJ;Thiele I;Alzheimer’s Disease Metabolomics Consortium;Kaddurah-Daouk R;Price ND
通讯作者：
Price ND