Open AccessMultiomics integrative analysis identifies APOE allele-specific blood biomarkers associated to Alzheimer’s disease etiopathogenesis
Author(s) -
Laura Madrid,
Sonia MorenoGrau,
Shahzad Ahmad,
Antonio GonzálezPérez,
Itziar de Rojas,
Rui Xia,
Pamela Victoria Martino Adami,
Pablo GarcíaGonzález,
Luca Kleineidam,
Qiong Yang,
Vincent Damotte,
Joshua C. Bis,
Fuensanta Noguera-Perea,
Céline Bellenguez,
Xueqiu Jian,
Juan Marín-Muñoz,
Benjamin GrenierBoley,
Adela Orellana,
M. Arfan Ikram,
Philippe Amouyel,
Claudia L. Satizábal,
Alzheimer’s Disease Neuroimaging Initiative,
Luis Miguel Real,
Carmen Antúnez-Almagro,
Anita L. DeStefano,
Alfredo Cabrera-Socorro,
Rebecca Sims,
Cornelia M. van Duijn,
Eric Boerwinkle,
Alfredo Ramı́rez,
Myriam Fornage,
JeanCharles Lambert,
Julie Williams,
Sudha Seshadri,
Janina S. Ried,
Agustín Ruiz,
María Eugenia Sáez
Publication year - 2021
Publication title -
aging
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.473
H-Index - 90
ISSN - 1945-4589
DOI - 10.18632/aging.202950
Subject(s) - apolipoprotein e , disease , concordance , allele , genome wide association study , dementia , alzheimer's disease , biology , omics , computational biology , biomarker , bioinformatics , medicine , genetics , gene , single nucleotide polymorphism , genotype
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.