Integrated lipidomics and proteomics network analysis highlights lipid and immunity pathways associated with Alzheimer's disease

作     者：Jin Xu Giulia Bankov Min Kim Asger Wretlind Jodie Lord Rebecca Green Angela Hodges Abdul Hye Dag Aarsland Latha Velayudhan Richard J.B.Dobson Petroula Proitsi Cristina Legido-Quigley on behalf of the AddNeuroMed Consortium 

作者机构：Institute of Pharmaceutical ScienceKing's College LondonLondonUK. Institute of PsychiatryPsychology&NeuroscienceKing's College LondonLondonUK. Steno Diabetes Center CopenhagenGentofteDenmark Center for Age Related MedicineStavanger University HospitalStavangerNorway 不详 

出 版 物：《Translational Neurodegeneration》 (转化神经变性病（英文）)

年 卷 期：2020年第9卷第3期

页      面：458-472页

核心收录：

学科分类：1002[医学-临床医学] 100203[医学-老年医学] 10[医学] 

基　　金：EU FP6 Mental Health Biomedical Research Centre King’s College London, KCL South London and Maudsley NHS Foundation Trust Sixth Framework Programme, FP6 National Institute for Health Research, NIHR Alzheimer’s Research UK, ARUK 

主　　题：Alzheimer's disease Dementia Brain atrophy sMRI Rate of cognitive decline Lipidomics Proteomics AD risk loci WGCNA 

摘      要：Background:There is an urgent need to understand the pathways and processes underlying Alzheimer s disease(AD)for early diagnosis and development of effective *** study was aimed to investigate Alzheimer s dementia using an unsupervised lipid,protein and gene multi-omics integrative ***:A lipidomics dataset comprising 185 AD patients,40 mild cognitive impairment(MCI)individuals and 185 controls,and two proteomics datasets(295 AD,159 MCI and 197 controls)were used for weighted gene CO-expression network analyses(WGCNA).Correlations of modules created within each modality with clinical AD diagnosis,brain atrophy measures and disease progression,as well as their correlations with each other,were *** ontology enrichment analysis was employed to examine the biological processes and molecular and cellular functions of protein modules associated with AD *** species were annotated in the lipid modules associated with AD *** associations between established AD risk loci and the lipid/protein modules that showed high correlation with AD phenotypes were also ***:Five of the 20 identified lipid modules and five of the 17 identified protein modules were correlated with clinical AD diagnosis,brain atrophy measures and disease *** lipid modules comprising phospholipids,triglycerides,sphingolipids and cholesterol esters were correlated with AD risk loci involved in immune response and lipid *** five protein modules involved in positive regulation of cytokine production,neutrophil-mediated immunity,and humoral immune responses were correlated with AD risk loci involved in immune and complement systems and in lipid metabolism(the APOE ε4 genotype).Conclusions:Modules of tightly regulated lipids and proteins,drivers in lipid homeostasis and innate immunity,are strongly associated with AD phenotypes.