title: Cross-region reduction in 5-hydroxymethylcytosine in Alzheimer's disease brain.
abstract: Epigenetic processes play a key role in the central nervous system and altered levels of 5-methylcytosine have been associated with a number of neurologic phenotypes, including Alzheimer's disease (AD). Recently, 3 additional cytosine modifications have been identified (5-hydroxymethylcytosine, 5-formylcytosine, and 5-carboxylcytosine), which are thought to be intermediate steps in the demethylation of 5-methylcytosine to unmodified cytosine. Little is known about the frequency of these modifications in the human brain during health or disease. In this study, we used immunofluorescence to confirm the presence of each modification in human brain and investigate their cross-tissue abundance in AD patients and elderly control samples. We identify a significant AD-associated decrease in global 5-hydroxymethylcytosine in entorhinal cortex and cerebellum, and differences in 5-formylcytosine levels between brain regions. Our study further implicates a role for epigenetic alterations in AD.
authors.affiliation: Institute of Psychiatry, King's College London, London, UK.
authors.forename: Daniel
authors.initials: D
authors.lastname: Condliffe
authors.affiliation: Institute of Psychiatry, King's College London, London, UK.
authors.forename: Andrew
authors.initials: A
authors.lastname: Wong
authors.affiliation: Institute of Psychiatry, King's College London, London, UK.
authors.forename: Claire
authors.initials: C
authors.lastname: Troakes
authors.affiliation: Institute of Psychiatry, King's College London, London, UK.
authors.forename: Petroula
authors.initials: P
authors.lastname: Proitsi
authors.affiliation: Institute of Psychiatry, King's College London, London, UK.
authors.forename: Yogen
authors.initials: Y
authors.lastname: Patel
authors.affiliation: Department of Psychiatry and Neuropsychology, School for Mental Health and Neuroscience, Maastricht University Medical Centre, Maastricht, the Netherlands.
authors.forename: Leonidas
authors.initials: L
authors.lastname: Chouliaras
authors.affiliation: Institute of Psychiatry, King's College London, London, UK.
authors.forename: Cathy
authors.initials: C
authors.lastname: Fernandes
authors.affiliation: Institute of Psychiatry, King's College London, London, UK.
authors.forename: Jonathan
authors.initials: J
authors.lastname: Cooper
authors.affiliation: Institute of Psychiatry, King's College London, London, UK.
authors.forename: Simon
authors.initials: S
authors.lastname: Lovestone
authors.affiliation: Institute of Psychiatry, King's College London, London, UK.
authors.forename: Leonard
authors.initials: L
authors.lastname: Schalkwyk
authors.affiliation: Institute of Psychiatry, King's College London, London, UK; Institute of Biomedical & Clinical Science, University of Exeter Medical School, University of Exeter, Devon, UK.
authors.forename: Jonathan
authors.initials: J
authors.lastname: Mill
authors.affiliation: Institute of Biomedical & Clinical Science, University of Exeter Medical School, University of Exeter, Devon, UK. Electronic address: k.lunnon@exeter.ac.uk.
authors.forename: Katie
authors.initials: K
authors.lastname: Lunnon
mesh_terms: D044503:5-Methylcytosine / Q000031:analogs & derivatives; D000368:Aged; D000369:Aged, 80 and over; D000544:Alzheimer Disease / Q000235:genetics* / Q000378:metabolism*; D001921:Brain / Q000378:metabolism*; D003596:Cytosine / Q000031:analogs & derivatives* / Q000378:metabolism; D044127:Epigenesis, Genetic / Q000235:genetics*; D005260:Female; D005455:Fluorescent Antibody Technique; D006801:Humans; D007559:Ivermectin / Q000031:analogs & derivatives; D008297:Male; D008745:Methylation
chemical_list: C560973:5-formylcytosine; C047538:demethylavermectins; C011865:5-hydroxymethylcytosine; D044503:5-Methylcytosine; D007559:Ivermectin; D003596:Cytosine
keywords: 5-caC; 5-carboxylcytosine; 5-fC; 5-formylcytosine; 5-hmC; 5-hydroxymethylcytosine; 5-mC; 5-methylcytosine; Alzheimer's disease; Brain; DNA methylation; Epigenetics