RT Journal Article
T1 Multiomics integrative analysis identifies APOE allele-specific blood biomarkers associated to Alzheimer's disease etiopathogenesis.
A1 Madrid, Laura
A1 Moreno-Grau, Sonia
A1 Ahmad, Shahzad
A1 González-Pérez, Antonio
A1 de Rojas, Itziar
A1 Xia, Rui
A1 Martino Adami, Pamela V
A1 García-González, Pablo
A1 Kleineidam, Luca
A1 Yang, Qiong
A1 Damotte, Vincent
A1 Bis, Joshua C
A1 Noguera-Perea, Fuensanta
A1 Bellenguez, Céline
A1 Jian, Xueqiu
A1 Marín-Muñoz, Juan
A1 Grenier-Boley, Benjamin
A1 Orellana, Adela
A1 Ikram, M Arfan
A1 Amouyel, Philippe
A1 Satizabal, Claudia L
A1 Alzheimer’s Disease Neuroimaging Initiative (ADNI)*, 
A1 EADI consortium, CHARGE consortium, GERAD consortium, GR@ACE/DEGESCO consortium
A1 Real, Luis Miguel
A1 Antúnez-Almagro, Carmen
A1 DeStefano, Anita
A1 Cabrera-Socorro, Alfredo
A1 Sims, Rebecca
A1 Van Duijn, Cornelia M
A1 Boerwinkle, Eric
A1 Ramírez, Alfredo
A1 Fornage, Myriam
A1 Lambert, Jean-Charles
A1 Williams, Julie
A1 Seshadri, Sudha
A1 ADAPTED consortium, 
A1 Ried, Janina S
A1 Ruiz, Agustín
A1 Saez, Maria Eugenia
K1 APOE
K1 Alzheimer’s disease
K1 biomarkers
K1 integrative analysis
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 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.
YR 2021
FD 2021-04-12
LK https://hdl.handle.net/10668/25121
UL https://hdl.handle.net/10668/25121
LA en
DS RISalud
RD Apr 6, 2025