Title | Multiomics integrative analysis identifies allele-specific blood biomarkers associated to Alzheimer's disease etiopathogenesis. |
Publication Type | Journal Article |
Year of Publication | 2021 |
Authors | Madrid L, Moreno-Grau S, Ahmad S, González-Perez 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, Sáez MEugenia |
Corporate Authors | Alzheimer’s Disease Neuroimaging Initiative(ADNI)*, EADI consortium, CHARGE consortium, GERAD consortium, GR@ACE/DEGESCO consortium, ADAPTED consortium |
Journal | Aging (Albany NY) |
Volume | 13 |
Issue | 7 |
Pagination | 9277-9329 |
Date Published | 2021 Apr 12 |
ISSN | 1945-4589 |
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. |
DOI | 10.18632/aging.202950 |
Pubmed Link | https://www.ncbi.nlm.nih.gov/pubmed/33846280?dopt=Abstract |
page_expo | External |
Alternate Journal | Aging (Albany NY) |
PubMed ID | 33846280 |
PubMed Central ID | PMC8064208 |
Grant List | R01 HL105756 / HL / NHLBI NIH HHS / United States |
Theme by Danetsoft and Danang Probo Sayekti inspired by Maksimer