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| 1 | Integrated lipidomics and proteomics network analysis highlights lipid and immunity pathways associated with Alzheimer's disease显示文摘Background:There is an urgent need to understand the pathways and processes underlying Alzheimer's disease(AD)for early diagnosis and development of effective treatments.This study was aimed to investigate Alzheimer's dementia using an unsupervised lipid,protein and gene multi-omics integrative approach.Methods: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 analyzed.Gene ontology enrichment analysis was employed to examine the biological processes and molecular and cellular functions of protein modules associated with AD phenotypes.Lipid species were annotated in the lipid modules associated with AD phenotypes.The associations between established AD risk loci and the lipid/protein modules that showed high correlation with AD phenotypes were also explored.Results: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 progression.The lipid modules comprising phospholipids,triglycerides,sphingolipids and cholesterol esters were correlated with AD risk loci involved in immune response and lipid metabolism.The 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. | 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 | 2020 | Translational Neurodegeneration2020，9，3： | 3 |
| 2 | Variation in DRD2 dopamine gene predicts extraverted personality显示文摘 | Smillie LD Cooper AJ Proitsi P | 2010 | Neurosci Lett2010，468，3： | 1 |
| 3 | Mitochondrial dysfunction and immune activation are detectable in early Alzheier's disease blood显示文摘 | Lurmon K Ibrahim Z Proitsi P | 2012 | J Alzheimers Dis2012，30，3： | 1 |
| 4 | Smell identification function as a severity and progression marker in Alzheimer’s disease显示文摘 | Latha Velayudhan Megan Pritchard John F. Powell Petroula Proitsi Simon Lovestone | 2013 | International Psychogeriatrics2013，，7： | 1 |
| 5 | Entorhinal Cortex Thickness Predicts Cognitive Decline in Alzheimer's Disease显示文摘 | Latha Velayudhan Petroula Proitsi Eric Westman J-Sebastian Muehlboeck Patrizia Mecocci Bruno Vellas Magda Tsolaki Iwona K&lstrok oszewska Hilkka Soininen Christian Spenger Angela Hodges John Powell Simon Lovestone Andrew Simmons | 2012 | Journal of Alzheimer's Disease2012，，3： | 1 |
| 6 | Alzheimer's disease suscepti- bility variants in the MS4A6A gene are associated with altered levels of MS4A6A expression in blood 显示文摘 | Proitsi P Lee SH Lunnon K | 2014 | Neurobiol Aging2014，35，2： | 1 |
| 7 | Candidate blood proteome markers of Alzheimer's disease onset and progression:a systematic review and replication study显示文摘 | Kiddle SJ Sattlecker M Proitsi P | 2014 | J Alzheimers Dis2014，38，3： | 1 |
| 8 | Deep sequencing of the Nicastrin gene in pooled DNA,the identification of genetic variants that affect risk of Alzheimer's disease显示文摘 | Lupton MK Proitsi P Danillidou M | 2011 | PLoS One2011，6，17： | 1 |
| 9 | Complement activation as a biomarker for Alzheimer' s disease 显示文摘 | Aiyaz M Lupton MK Proitsi P | 2012 | Immunobiology2012，217，2： | 1 |
| 10 | Entorhinal Cortex Thickness Predicts Cognitive Decline in Alzheimer's Disease显示文摘 | Velayudhan L Proitsi P Westman E | | 0，，： | 1 |
| 11 | Complement activation as a biomarker for Alzheimer's disease显示文摘 | Aiyaz M Lupton MK Proitsi P | 2012 | Immunobiology2012，217，2： | 1 |
| 12 | Mitochondrial dysfunction and immune activation are detectable in early Alzheimer′s disease blood显示文摘 | Lunnon K Ibrahim Z Proitsi P | 2012 | J Alzheimers Dis2012，30，3： | 1 |
| 13 | A multiple indicators multiple eanses(MIMIC) model of behavioural and psyehologieal symptoms in dementia(BPSD) 显示文摘 | Proitsi P Hamilton G Tsolaki M | 2011 | Neurobiol Aging2011，32，： | 1 |
| 14 | Positional Pathway Screen of wnt signaling genes in schizophrenia: association with DKK4 显示文摘 | Proitsi P Li T Hamilton G | 2008 | Bio Psychiatry2008，63，1： | 1 |
| 15 | A multiple indicators multiple causes (MIMIC)model of behavioural and psychological symptoms in dementia (BPSD)显示文摘 | Proitsi P Hamilton G Tsolaki M | 2011 | Neurobiology of Aging2011，32，3： | 1 |
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