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Epigenetic signatures of methylated DNA cytosine in Alzheimer's disease.
Fetahu, Irfete S; Ma, Dingailu; Rabidou, Kimberlie; Argueta, Christian; Smith, Michael; Liu, Hang; Wu, Feizhen; Shi, Yujiang G.
Afiliación
  • Fetahu IS; Division of Endocrinology, Diabetes and Hypertension, Department of Medicine, Brigham and Women's Hospital, Boston, MA 02115, USA.
  • Ma D; Harvard Medical School, Boston, MA 02115, USA.
  • Rabidou K; Division of Endocrinology, Diabetes and Hypertension, Department of Medicine, Brigham and Women's Hospital, Boston, MA 02115, USA.
  • Argueta C; Laboratory of Epigenetics, Institutes of Biomedical Sciences, Shanghai Medical College of Fudan University, Shanghai 200032, China.
  • Smith M; Division of Endocrinology, Diabetes and Hypertension, Department of Medicine, Brigham and Women's Hospital, Boston, MA 02115, USA.
  • Liu H; Division of Endocrinology, Diabetes and Hypertension, Department of Medicine, Brigham and Women's Hospital, Boston, MA 02115, USA.
  • Wu F; Harvard Medical School, Boston, MA 02115, USA.
  • Shi YG; Division of Endocrinology, Diabetes and Hypertension, Department of Medicine, Brigham and Women's Hospital, Boston, MA 02115, USA.
Sci Adv ; 5(8): eaaw2880, 2019 08.
Article en En | MEDLINE | ID: mdl-31489368
Alzheimer's disease (AD), a progressive neurodegenerative disorder, is the most common untreatable form of dementia. Identifying molecular biomarkers that allow early detection remains a key challenge in the diagnosis, treatment, and prognostic evaluation of the disease. Here, we report a novel experimental and analytical model characterizing epigenetic alterations during AD onset and progression. We generated the first integrated base-resolution genome-wide maps of the distribution of 5-methyl-cytosine (5mC), 5-hydroxymethyl-cytosine (5hmC), and 5-formyl/carboxy-cytosine (5fC/caC) in normal and AD neurons. We identified 27 AD region-specific and 39 CpG site-specific epigenetic signatures that were independently validated across our familial and sporadic AD models, and in an independent clinical cohort. Thus, our work establishes a new model and strategy to study the epigenetic alterations underlying AD onset and progression and provides a set of highly reliable AD-specific epigenetic signatures that may have early diagnostic and prognostic implications.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: ADN / Metilación de ADN / Epigénesis Genética / Enfermedad de Alzheimer Tipo de estudio: Prognostic_studies / Screening_studies Límite: Aged / Female / Humans / Male Idioma: En Revista: Sci Adv Año: 2019 Tipo del documento: Article País de afiliación: Estados Unidos Pais de publicación: Estados Unidos
Texto completo
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: ADN / Metilación de ADN / Epigénesis Genética / Enfermedad de Alzheimer Tipo de estudio: Prognostic_studies / Screening_studies Límite: Aged / Female / Humans / Male Idioma: En Revista: Sci Adv Año: 2019 Tipo del documento: Article País de afiliación: Estados Unidos Pais de publicación: Estados Unidos