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Dysregulated expression levels of APH1B in peripheral blood are associated with brain atrophy and amyloid-β deposition in Alzheimer’s disease

Research output: Contribution to journalArticlepeer-review

for the AddNeuroMed consortium and the Alzheimer’s Disease Neuroimaging Initiative

Original languageEnglish
Article number183
Number of pages1
JournalAlzheimer's Research and Therapy
Volume13
Issue number1
Early online date3 Nov 2021
DOIs
E-pub ahead of print3 Nov 2021
PublishedDec 2021

Bibliographical note

Funding Information: Data collection and sharing for this project was funded by the Alzheimer’s Disease Neuroimaging Initiative (National Institutes of Health Grant U01 AG024904) and DOD ADNI (Department of Defense award number W81XWH-12-2-0012). ADNI is funded by the National Institute on Aging, the National Institute of Biomedical Imaging and Bioengineering, and through generous contributions from the following: AbbVie, Alzheimer’s Association; Alzheimer’s Drug Discovery Foundation; Araclon Biotech; BioClinica, Inc.; Biogen; Bristol-Myers Squibb Company; CereSpir, Inc.; Cogstate; Eisai Inc.; Elan Pharmaceuticals, Inc.; Eli Lilly and Company; EuroImmun; F. Hoffmann-La Roche Ltd. and its affiliated company Genentech, Inc.; Fujirebio; GE Healthcare; IXICO Ltd.; Janssen Alzheimer Immunotherapy Research & Development, LLC.; Johnson & Johnson Pharmaceutical Research & Development LLC.; Lumosity; Lundbeck; Merck & Co., Inc.; Meso Scale Diagnostics, LLC.; NeuroRx Research; Neurotrack Technologies; Novartis Pharmaceuticals Corporation; Pfizer Inc.; Piramal Imaging; Servier; Takeda Pharmaceutical Company; and Transition Therapeutics. The Canadian Institutes of Health Research is providing funds to support ADNI clinical sites in Canada. Private sector contributions are facilitated by the Foundation for the National Institutes of Health ( www.fnih.org ). The grantee organization is the Northern California Institute for Research and Education, and the study is coordinated by the Alzheimer’s Therapeutic Research Institute at the University of Southern California. ADNI data are disseminated by the Laboratory for Neuro Imaging at the University of Southern California. The collection and analysis of AddNeuroMed samples was supported by InnoMed (Innovative Medicines in Europe) an Integrated Project funded by the European Union of the Sixth Framework program priority FP6–2004-LIFESCIHEALTH-5, the Alzheimer’s Research Trust, the John and Lucille van Geest Foundation, and the NIHR Biomedical Research Centre for Mental Health at the South London and Maudsley NHS Foundation Trust and [Institute of Psychiatry] Kings College London. Funding Information: This work was supported by the National Research Foundation of Korea grant funded by the Korean government (Ministry of Science and ICT) (No. 2020R1C1C1013718). The Medical Research Collaborating Center of Seoul National University Bundang Hospital contributed to statistical analyses. Funding Information: This work was supported by the National Research Foundation of Korea grant funded by the Korean government (Ministry of Science and ICT) (No. 2020R1C1C1013718). The Medical Research Collaborating Center of Seoul National University Bundang Hospital contributed to statistical analyses. Publisher Copyright: © 2021, The Author(s).

King's Authors

Abstract

Background: The interaction between the brain and periphery might play a crucial role in the development of Alzheimer’s disease (AD). Methods: Using blood transcriptomic profile data from two independent AD cohorts, we performed expression quantitative trait locus (cis-eQTL) analysis of 29 significant genetic loci from a recent large-scale genome-wide association study to investigate the effects of the AD genetic variants on gene expression levels and identify their potential target genes. We then performed differential gene expression analysis of identified AD target genes and linear regression analysis to evaluate the association of differentially expressed genes with neuroimaging biomarkers. Results: A cis-eQTL analysis identified and replicated significant associations in seven genes (APH1B, BIN1, FCER1G, GATS, MS4A6A, RABEP1, TRIM4). APH1B expression levels in the blood increased in AD and were associated with entorhinal cortical thickness and global cortical amyloid-β deposition. Conclusion: An integrative analysis of genetics, blood-based transcriptomic profiles, and imaging biomarkers suggests that APH1B expression levels in the blood might play a role in the pathogenesis of AD.

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