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Sci Adv. 2019 Aug 28;5(8):eaaw2880. doi: 10.1126/sciadv.aaw2880. eCollection 2019 Aug.

Epigenetic signatures of methylated DNA cytosine in Alzheimer's disease.

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Division of Endocrinology, Diabetes and Hypertension, Department of Medicine, Brigham and Women's Hospital, Boston, MA 02115, USA.
Harvard Medical School, Boston, MA 02115, USA.
Laboratory of Epigenetics, Institutes of Biomedical Sciences, Shanghai Medical College of Fudan University, Shanghai 200032, China.
Department of Biostatistics and Computational Biology, Dana-Farber Cancer Institute, Boston, MA 02115, USA.


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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