Liquid biopsy in alzheimer's disease patients reveals epigenetic changes in the PRLHR gene
Fecha
2023Autor
Versión
Acceso abierto / Sarbide irekia
Tipo
Artículo / Artikulua
Versión
Versión publicada / Argitaratu den bertsioa
Identificador del proyecto
Impacto
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10.3390/cells12232679
Resumen
In recent years, new DNA methylation variants have been reported in genes biologically relevant to Alzheimer’s disease (AD) in human brain tissue. However, this AD-specific epigenetic information remains brain-locked and unreachable during patients’ lifetimes. In a previous methylome performed in the hippocampus of 26 AD patients and 12 controls, we found higher methylation levels in AD patients ...
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In recent years, new DNA methylation variants have been reported in genes biologically relevant to Alzheimer’s disease (AD) in human brain tissue. However, this AD-specific epigenetic information remains brain-locked and unreachable during patients’ lifetimes. In a previous methylome performed in the hippocampus of 26 AD patients and 12 controls, we found higher methylation levels in AD patients in the promoter region of PRLHR, a gene involved in energy balance regulation. Our aim was to further characterize PRLHR’s role in AD and to evaluate if the liquid biopsy technique would provide life access to this brain information in a non-invasive way. First, we extended the methylation mapping of PRLHR and validated previous methylome results via bisulfite cloning sequencing. Next, we observed a positive correlation between PRLHR methylation levels and AD-related neuropathological changes and a decreased expression of PRLHR in AD hippocampus. Then, we managed to replicate the hippocampal methylation differences in plasma cfDNA from an additional cohort of 35 AD patients and 35 controls. The isolation of cfDNA from the plasma of AD patients may constitute a source of potential epigenetic biomarkers to aid AD clinical management. [--]
Materias
450K array,
Alzheimer's disease,
Cell-free DNA,
DNA methylation,
Liquid biopsy,
PRLHR,
Prolactin releasing-peptide (PrRP)
Editor
MDPI
Publicado en
Cells 2023, 12(23), 2679
Departamento
Universidad Pública de Navarra. Departamento de Ciencias de la Salud /
Nafarroako Unibertsitate Publikoa. Osasun Zientziak Saila
Versión del editor
Entidades Financiadoras
The authors sincerely appreciate funding support by the Government of Navarra [G°Na 36/18], by the Spanish Government through a grant from the Institute of Health Carlos III (FIS PI20/01701), jointly funded by the European Regional Development Fund (ERDF), European Union, A way of shaping Europe. The project leading to these results has received funding from “la Caixa” Foundation (ID 100010434) co-funded by Fundación Luzón (HR20-01109_BIOP-ALS). In addition, B.A. is supported by a PFIS fellowship from the Spanish Government (FI18/00150), M.M. (Mónica Macías) is beneficiary of a grant “Río Hortega” from the Spanish Government (CM20/00240), A.U.-C. received a grant Doctorandos industriales 2018–2020 and a Predoctoral grant (2019) funded by the Department of Industry and Health of the Government of Navarra, M.M. (Maite Mendioroz) received a grant Contrato de intensificación from the Institute of Health Carlos III (INT19/00029) and a grant (LCF/PR/PR15/51100006) funded by LaCaixa Foundation.