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Multiomics integrative analysis identifies allele-specific blood biomarkers associated to Alzheimer's disease etiopathogenesis.

TitleMultiomics integrative analysis identifies allele-specific blood biomarkers associated to Alzheimer's disease etiopathogenesis.
Publication TypeJournal Article
Year of Publication2021
AuthorsMadrid L, Moreno-Grau S, Ahmad S, González-Pérez A, de Rojas I, Xia R, Adami PVMartino, García-González P, Kleineidam L, Yang Q, Damotte V, Bis JC, Noguera-Perea F, Bellenguez C, Jian X, Marín-Muñoz J, Grenier-Boley B, Orellana A, M Ikram A, Amouyel P, Satizabal CL, Real LMiguel, Antúnez-Almagro C, Destefano A, Cabrera-Socorro A, Sims R, van Duijn CM, Boerwinkle E, Ramirez A, Fornage M, Lambert J-C, Williams J, Seshadri S, Ried JS, Ruiz A, Saez MEugenia
Corporate AuthorsAlzheimer’s Disease Neuroimaging Initiative(ADNI)*, EADI consortium, CHARGE consortium, GERAD consortium, GR@ACE/DEGESCO consortium, ADAPTED consortium
JournalAging (Albany NY)
Volume13
Issue7
Pagination9277-9329
Date Published2021 Apr 12
ISSN1945-4589
Abstract

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 haplotype ( and ). 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 and 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.

DOI10.18632/aging.202950
Alternate JournalAging (Albany NY)
PubMed ID33846280
PubMed Central IDPMC8064208
Grant ListR01 HL105756 / HL / NHLBI NIH HHS / United States