TY - JOUR
T1 - Multiomics integrative analysis identifies APOE allele-specific blood biomarkers associated to Alzheimer’s disease etiopathogenesis
AU - Madrid, Laura
AU - Moreno-Grau, Sonia
AU - Ahmad, Shahzad
AU - González-Pérez, Antonio
AU - de Rojas, Itziar
AU - Xia, Rui
AU - Adami, Pamela V.Martino
AU - García-González, Pablo
AU - Kleineidam, Luca
AU - Yang, Qiong
AU - Damotte, Vincent
AU - Bisl, Joshua C.
AU - Noguera-Perea, Fuensanta
AU - Bellenguez, Céline
AU - Jian, Xueqiu
AU - Marín-Muñoz, Juan
AU - Grenier-Boley, Benjamin
AU - Orellana, Adela
AU - Ikram, M. Arfan
AU - Amouye, Philippe
AU - Satizabal, Claudia L.
AU - Real, Luis Miguel
AU - Antúnez-Almagro, Carmen
AU - DeStefano, Anita
AU - Cabrera-Socorro, Alfredo
AU - Sims, Rebecca
AU - Duijn, Cornelia M.Van
AU - Boerwinkle, Eric
AU - Ramírez, Alfredo
AU - Fornage, Myriam
AU - Lambert, Jean Charles
AU - Williams, Julie
AU - Seshadri, Sudha
AU - Ried, Janina S.
AU - Ruiz, Agustín
AU - Saez, Maria Eugenia
N1 - Publisher Copyright:
© 2021 Madrid et al. This is an open access article distributed under the terms of the Creative Commons Attribution License (CC BY 3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
PY - 2021/4/15
Y1 - 2021/4/15
N2 - Alzheimer’s disease (AD) is the most common form of dementia, currently affecting 35 million people worldwide. Apolipoprotein E (APOE) ε4 allele is the major risk factor for sporadic, late-onset AD (LOAD), which comprises over 95% of AD cases, increasing the risk of AD 4-12 fold. Despite this, the role of APOE in AD pathogenesis is still a mystery. Aiming for a better understanding of APOE-specific effects, the ADAPTED consortium analyzed and integrated publicly available data of multiple OMICS technologies from both plasma and brain stratified by APOE haplotype (APOE2, APOE3 and APOE4). Combining genome-wide association studies (GWAS) with differential mRNA and protein expression analyses and single-nuclei transcriptomics, we identified genes and pathways contributing to AD in both APOE dependent and independent fashion. Interestingly, we characterized a set of biomarkers showing plasma and brain consistent protein profiles and opposite trends in APOE2 and APOE4 AD cases that could constitute screening tools for a disease that lacks specific blood biomarkers. Beside the identification of APOE-specific signatures, our findings advocate that this novel approach, based on the concordance across OMIC layers and tissues, is an effective strategy for overcoming the limitations of often underpowered single-OMICS studies.
AB - Alzheimer’s disease (AD) is the most common form of dementia, currently affecting 35 million people worldwide. Apolipoprotein E (APOE) ε4 allele is the major risk factor for sporadic, late-onset AD (LOAD), which comprises over 95% of AD cases, increasing the risk of AD 4-12 fold. Despite this, the role of APOE in AD pathogenesis is still a mystery. Aiming for a better understanding of APOE-specific effects, the ADAPTED consortium analyzed and integrated publicly available data of multiple OMICS technologies from both plasma and brain stratified by APOE haplotype (APOE2, APOE3 and APOE4). Combining genome-wide association studies (GWAS) with differential mRNA and protein expression analyses and single-nuclei transcriptomics, we identified genes and pathways contributing to AD in both APOE dependent and independent fashion. Interestingly, we characterized a set of biomarkers showing plasma and brain consistent protein profiles and opposite trends in APOE2 and APOE4 AD cases that could constitute screening tools for a disease that lacks specific blood biomarkers. Beside the identification of APOE-specific signatures, our findings advocate that this novel approach, based on the concordance across OMIC layers and tissues, is an effective strategy for overcoming the limitations of often underpowered single-OMICS studies.
KW - APOE
KW - Alzheimer’s disease
KW - biomarkers
KW - integrative analysis
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U2 - 10.18632/aging.202950
DO - 10.18632/aging.202950
M3 - Article
C2 - 33846280
AN - SCOPUS:85104714128
SN - 1945-4589
VL - 13
SP - 9277
EP - 9329
JO - Aging
JF - Aging
IS - 7
ER -