Multiomics profiling of human plasma and cerebrospinal fluid reveals ATN‐derived networks and highlights causal links in Alzheimer's disease
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| Title: | Multiomics profiling of human plasma and cerebrospinal fluid reveals ATN‐derived networks and highlights causal links in Alzheimer's disease |
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| Authors: | Shi, Liu, Xu, Jin, Green, Rebecca, Wretlind, Asger, Homann, Jan, Buckley, Noel J, Tijms, Betty M, Vos, Stephanie JB, Lill, Christina M, Kate, Mara Ten, Engelborghs, Sebastiaan, Sleegers, Kristel, Frisoni, Giovanni B, Wallin, Anders, Lleó, Alberto, Popp, Julius, Martinez-Lage, Pablo, Streffer, Johannes, Barkhof, Frederik, Zetterberg, Henrik, Visser, Pieter Jelle, Lovestone, Simon, Bertram, Lars, Nevado-Holgado, Alejo J, Proitsi, Petroula, Legido-Quigley, Cristina |
| Contributors: | Universitat Autònoma de Barcelona, Brussels Heritage Lab, Clinical sciences, FORMER_Neuroprotection & Neuromodulation, Neurology, Neuroprotection & Neuromodulation |
| Source: | Alzheimers & Dementia r-IIB SANT PAU. Repositorio Institucional de Producción Científica del Instituto de Investigación Biomédica Sant Pau Institut dInvestigació Biomèdica Sant Pau (IIB Sant Pau) Dipòsit Digital de Documents de la UAB Universitat Autònoma de Barcelona Shi, L, Xu, J, Green, R, Wretlind, A, Homann, J, Buckley, N J, Tijms, B M, Vos, S J B, Lill, C M, Kate, M T, Engelborghs, S, Sleegers, K, Frisoni, G B, Wallin, A, Lleó, A, Popp, J, Martinez-Lage, P, Streffer, J, Barkhof, F, Zetterberg, H, Visser, P J, Lovestone, S, Bertram, L, Nevado-Holgado, A J, Proitsi, P & Legido-Quigley, C 2023, 'Multiomics profiling of human plasma and cerebrospinal fluid reveals ATN-derived networks and highlights causal links in Alzheimer's disease', Alzheimer's and Dementia, vol. 19, no. 8, pp. 3350-3364. https://doi.org/10.1002/alz.12961 Alzheimer's & dementia, vol. 19, no. 8, pp. 3350-3364 Alzheimer's & dementia |
| Publisher Information: | Wiley, 2023. |
| Publication Year: | 2023 |
| Subject Terms: | LOCI, AT(N) framework, BETA, PROGRESSION, tau Proteins, 03 medical and health sciences, 0302 clinical medicine, Polygenic risk score, Alzheimer Disease, Mendelian randomization, multimodal biomarker, Humans, Cognitive Dysfunction, OXIDATIVE STRESS, Multi-omics, Amyloid beta-Peptides/cerebrospinal fluid, tau Proteins/cerebrospinal fluid, Multiomics, Biomarkers/cerebrospinal fluid, Cognitive Dysfunction/cerebrospinal fluid, Peptide Fragments/cerebrospinal fluid, Alzheimer's disease, multi-omics, polygenic risk score, Amyloid beta-Peptides, PATHWAYS, FRAMEWORK, Peptide Fragments, 3. Good health, Multimodal biomarker, Human medicine, Biomarkers |
| Description: | IntroductionThis study employed an integrative system and causal inference approach to explore molecular signatures in blood and CSF, the amyloid/tau/neurodegeneration [AT(N)] framework, mild cognitive impairment (MCI) conversion to Alzheimer's disease (AD), and genetic risk for AD.MethodsUsing the European Medical Information Framework (EMIF)‐AD cohort, we measured 696 proteins in cerebrospinal fluid (n = 371), 4001 proteins in plasma (n = 972), 611 metabolites in plasma (n = 696), and genotyped whole‐blood (7,778,465 autosomal single nucleotide epolymorphisms, n = 936). We investigated associations: molecular modules to AT(N), module hubs with AD Polygenic Risk scores and APOE4 genotypes, molecular hubs to MCI conversion and probed for causality with AD using Mendelian randomization (MR).ResultsAT(N) framework associated with protein and lipid hubs. In plasma, Proprotein Convertase Subtilisin/Kexin Type 7 showed evidence for causal associations with AD. AD was causally associated with Reticulocalbin 2 and sphingomyelins, an association driven by the APOE isoform.DiscussionThis study reveals multi‐omics networks associated with AT(N) and causal AD molecular candidates. |
| Document Type: | Article |
| File Description: | application/pdf |
| Language: | English |
| ISSN: | 1552-5279 1552-5260 |
| DOI: | 10.1002/alz.12961 |
| Access URL: | https://pubmed.ncbi.nlm.nih.gov/36790009 https://iibsantpau.fundanetsuite.com/Publicaciones/ProdCientif/PublicacionFrw.aspx?id=15689 https://cris.maastrichtuniversity.nl/en/publications/9333efe7-e7b0-470a-8b98-7882c03d1da7 https://doi.org/10.1002/alz.12961 https://research.vumc.nl/en/publications/611c1de7-f35a-47d5-b856-071f55702665 https://pure.amsterdamumc.nl/en/publications/7f3f1f9b-60de-484c-b588-1838450ecf61 https://doi.org/10.1002/alz.12961 http://nbn-resolving.org/urn/resolver.pl?urn=urn:nbn:ch:serval-BIB_C8A230E9823A9 https://serval.unil.ch/resource/serval:BIB_C8A230E9823A.P001/REF.pdf https://serval.unil.ch/notice/serval:BIB_C8A230E9823A https://hdl.handle.net/10067/1952260151162165141 https://repository.uantwerpen.be/docstore/d:irua:16859 https://biblio.vub.ac.be/vubir/multiomics-profiling-of-human-plasma-and-cerebrospinal-fluid-reveals-atnderived-networks-and-highlights-causal-links-in-alzheimers-disease(9c102c8c-6ae2-40d1-b18d-27b2df2b0ef0).html https://discovery-pp.ucl.ac.uk/id/eprint/10165360/ |
| Rights: | CC BY NC ND CC BY |
| Accession Number: | edsair.doi.dedup.....a34d4c5501fa8a6cd064e1b903e97322 |
| Database: | OpenAIRE |
Nájsť tento článok vo Web of Science | Abstract: | IntroductionThis study employed an integrative system and causal inference approach to explore molecular signatures in blood and CSF, the amyloid/tau/neurodegeneration [AT(N)] framework, mild cognitive impairment (MCI) conversion to Alzheimer's disease (AD), and genetic risk for AD.MethodsUsing the European Medical Information Framework (EMIF)‐AD cohort, we measured 696 proteins in cerebrospinal fluid (n = 371), 4001 proteins in plasma (n = 972), 611 metabolites in plasma (n = 696), and genotyped whole‐blood (7,778,465 autosomal single nucleotide epolymorphisms, n = 936). We investigated associations: molecular modules to AT(N), module hubs with AD Polygenic Risk scores and APOE4 genotypes, molecular hubs to MCI conversion and probed for causality with AD using Mendelian randomization (MR).ResultsAT(N) framework associated with protein and lipid hubs. In plasma, Proprotein Convertase Subtilisin/Kexin Type 7 showed evidence for causal associations with AD. AD was causally associated with Reticulocalbin 2 and sphingomyelins, an association driven by the APOE isoform.DiscussionThis study reveals multi‐omics networks associated with AT(N) and causal AD molecular candidates. |
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| ISSN: | 15525279 15525260 |
| DOI: | 10.1002/alz.12961 |