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Lead-exposure associated miRNAs in humans and Alzheimer’s disease as potential biomarkers of the disease and disease processes
Department of Toxicogenomics, Maastricht University, Universiteitssingel 50, Maastricht, Netherlands; MHeNS, School for Mental Health and Neuroscience, Maastricht University, Universiteitssingel 50, Maastricht, Netherlands.
Department of Toxicogenomics, Maastricht University, Universiteitssingel 50, Maastricht, Netherlands; MHeNS, School for Mental Health and Neuroscience, Maastricht University, Universiteitssingel 50, Maastricht, Netherlands.
Department of Biomedical Sciences, Institute Born-Bunge, University of Antwerp, Universiteitsplein 1, Antwerpen, Belgium; Neuroprotection and Neuromodulation (NEUR), Center for Neurosciences (C4N), Vrije Universiteit Brussel (VUB), Laarbeeklaan 103, Brussel, Belgium; Department of Neurology, and Brussels Integrated Center for Brain and Memory (Bru-BRAIN), Universitair Ziekenhuis Brussel (UZ Brussel), Laarbeeklaan 101, Brussel, Belgium.
Department of Toxicogenomics, Maastricht University, Universiteitssingel 50, Maastricht, Netherlands.
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2022 (English)In: Scientific Reports, E-ISSN 2045-2322, Vol. 12, no 1, article id 15966Article in journal (Refereed) Published
Abstract [en]

Alzheimer’s disease (AD) is a neurodegenerative disease that eventually affects memory and behavior. The identification of biomarkers based on risk factors for AD provides insight into the disease since the exact cause of AD remains unknown. Several studies have proposed microRNAs (miRNAs) in blood as potential biomarkers for AD. Exposure to heavy metals is a potential risk factor for onset and development of AD. Blood cells of subjects that are exposed to lead detected in the circulatory system, potentially reflect molecular responses to this exposure that are similar to the response of neurons. In this study we analyzed blood cell-derived miRNAs derived from a general population as proxies of potentially AD-related mechanisms triggered by lead exposure. Subsequently, we analyzed these mechanisms in the brain tissue of AD subjects and controls. A total of four miRNAs were identified as lead exposure-associated with hsa-miR-3651, hsa-miR-150-5p and hsa-miR-664b-3p being negatively and hsa-miR-627 positively associated. In human brain derived from AD and AD control subjects all four miRNAs were detected. Moreover, two miRNAs (miR-3651, miR-664b-3p) showed significant differential expression in AD brains versus controls, in accordance with the change direction of lead exposure. The miRNAs’ gene targets were validated for expression in the human brain and were found enriched in AD-relevant pathways such as axon guidance. Moreover, we identified several AD relevant transcription factors such as CREB1 associated with the identified miRNAs. These findings suggest that the identified miRNAs are involved in the development of AD and might be useful in the development of new, less invasive biomarkers for monitoring of novel therapies or of processes involved in AD development.

Place, publisher, year, edition, pages
Nature Publishing Group, 2022. Vol. 12, no 1, article id 15966
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Neurosciences
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URN: urn:nbn:se:umu:diva-200102DOI: 10.1038/s41598-022-20305-5PubMedID: 36153426Scopus ID: 2-s2.0-85138460597OAI: oai:DiVA.org:umu-200102DiVA, id: diva2:1703201
Available from: 2022-10-12 Created: 2022-10-12 Last updated: 2022-10-12Bibliographically approved

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Bergdahl, Ingvar

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