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Differential DNA methylation of the genes for amyloid precursor protein, tau and neurofilaments in human traumatic brain injury
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Enblad: Neurosurgery.ORCID iD: 0000-0001-6173-8357
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Schiöth: Functional Pharmacology.ORCID iD: 0000-0001-6377-0270
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Pharmaceutical Biosciences.ORCID iD: 0000-0002-2451-4386
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Pharmaceutical Biosciences.
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2021 (English)In: Journal of Neurotrauma, ISSN 0897-7151, E-ISSN 1557-9042, Vol. 38, no 12, p. 1679-1688Article in journal (Refereed) Published
Abstract [en]

Traumatic brain injury (TBI) is an established risk factor for neurodegenerative disorders and dementias. Epigenetic modifications, such as DNA methylation, may alter the expression of genes without altering the DNA sequence in response to environmental factors. We hypothesized that DNA methylation changes may occur in the injured human brain and be implicated in the neurodegenerative aftermath of TBI. The DNA methylation status of genes related to neurodegeneration, e.g. amyloid beta precursor protein (APP), microtubule associated protein tau (MAPT), neurofilament heavy (NEFH), neurofilament medium (NEFM) and neurofilament light (NEFL), was analyzed in fresh, surgically resected human brain tissue from 17 severe TBI patients and compared with brain biopsy samples from 19 patients with idiopathic normal pressure hydrocephalus (iNPH). We also performed an epigenome-wide association study (EWAS) comparing TBI patients to iNPH controls. Thirty-eight CpG sites in the APP, MAPT, NEFH and NEFL genes were differentially methylated by TBI. Among the top 20 differentially methylated CpG sites, 11 were in the APP gene. In addition, the EWAS evaluating 828 888 CpG sites revealed 308 differentially methylated CpG sites in genes related to cellular/anatomical structure development, cell differentiation and anatomical morphogenesis. These preliminary findings provide the first evidence of an altered DNA methylome in the injured human brain and may have implications for the neurodegenerative disorders associated at long-term with TBI. 

Place, publisher, year, edition, pages
Mary Ann Liebert, 2021. Vol. 38, no 12, p. 1679-1688
Keywords [en]
amyloid beta precursor protein, DNA methylation, epigenome-wide association study tau, traumatic brain injury
National Category
Pharmaceutical Sciences
Identifiers
URN: urn:nbn:se:uu:diva-428785DOI: 10.1089/neu.2020.7283ISI: 000606620000001PubMedID: 33191850OAI: oai:DiVA.org:uu-428785DiVA, id: diva2:1510443
Funder
Swedish Research Council, 2014-07550Swedish Research Council, 2018-0500Available from: 2020-12-16 Created: 2020-12-16 Last updated: 2024-01-15Bibliographically approved

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Abu Hamdeh, SamiCiuculete, Diana-MariaSarkisyan, DaniilIngelsson, MartinSchiöth, Helgi B.
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Enblad: NeurosurgerySchiöth: Functional PharmacologyDepartment of Pharmaceutical BiosciencesGeriatrics
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