%0 Journal Article
%A Madrid, Laura
%A Moreno-Grau, Sonia
%A Ahmad, Shahzad
%A González-Pérez, Antonio
%A de Rojas, Itziar
%A Xia, Rui
%A Martino Adami, Pamela V
%A García-González, Pablo
%A Kleineidam, Luca
%A Yang, Qiong
%A Damotte, Vincent
%A Bis, Joshua C
%A Noguera-Perea, Fuensanta
%A Bellenguez, Céline
%A Jian, Xueqiu
%A Marín-Muñoz, Juan
%A Grenier-Boley, Benjamin
%A Orellana, Adela
%A Ikram, M Arfan
%A Amouyel, Philippe
%A Satizabal, Claudia L
%A Alzheimer’s Disease Neuroimaging Initiative (ADNI)*
%A EADI consortium, CHARGE consortium, GERAD consortium, GR@ACE/DEGESCO consortium
%A Real, Luis Miguel
%A Antúnez-Almagro, Carmen
%A DeStefano, Anita
%A Cabrera-Socorro, Alfredo
%A Sims, Rebecca
%A Van Duijn, Cornelia M
%A Boerwinkle, Eric
%A Ramírez, Alfredo
%A Fornage, Myriam
%A Lambert, Jean-Charles
%A Williams, Julie
%A Seshadri, Sudha
%A ADAPTED consortium
%A Ried, Janina S
%A Ruiz, Agustín
%A Saez, Maria Eugenia
%T Multiomics integrative analysis identifies APOE allele-specific blood biomarkers associated to Alzheimer's disease etiopathogenesis.
%D 2021
%U https://hdl.handle.net/10668/25121
%X 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 analysed 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 characterised 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.
%K APOE
%K Alzheimer’s disease
%K biomarkers
%K integrative analysis
%~