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

Madrid, Laura, Moreno-Grau, Sonia, Ahmad, Shahzad, González-Pérez, Antonio, de Rojas, Itziar, Xia, Rui, Martino Adami, Pamela V., García-González, Pablo, Kleineidam, Luca, Yang, Qiong, Damotte, Vincent, Bis, Joshua C., Noguera-Perea, Fuensanta, Bellenguez, Céline, Jian, Xueqiu, Marín-Muñoz, Juan, Grenier-Boley, Benjamin, Orellana, Adela, Ikram, M. Arfan, Amouyel, Philippe, Satizabal, Claudia L., Real, Luis Miguel, Antúnez-Almagro, Carmen, DeStefano, Anita, Cabrera-Socorro, Alfredo, Sims, Rebecca, Van Duijn, Cornelia M., Boerwinkle, Eric, Ramírez, Alfredo, Fornage, Myriam, Lambert, Jean-Charles, Williams, Julie, Seshadri, Sudha, Ried, Janina S., Ruiz, Agustín and Saez, Maria Eugenia 2022. Multiomics integrative analysis identifies APOE allele-specific blood biomarkers associated to Alzheimer's disease etiopathogenesis. Aging 13 (7) , pp. 9277-9329. 10.18632/aging.202950

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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 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.

Item Type: Article
Date Type: Publication
Status: Published
Schools: Medicine
MRC Centre for Neuropsychiatric Genetics and Genomics (CNGG)
Additional Information: This is an open access article distributed under the terms of the Creative Commons Attribution License (CC BY 3.0)
Publisher: Impact Journals
ISSN: 1945-4589
Date of First Compliant Deposit: 4 May 2022
Date of Acceptance: 26 March 2021
Last Modified: 30 Jun 2022 08:34
URI: https://orca.cardiff.ac.uk/id/eprint/149526

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