title: Alterations in global DNA methylation and hydroxymethylation are not detected in Alzheimer's disease.
abstract: OBJECTIVE
  Genetic factors do not seem to account fully for Alzheimer disease (AD) pathogenesis. There is evidence for the contribution of environmental factors, whose effect may be mediated by epigenetic mechanisms. Epigenetics involves the regulation of gene expression independently of DNA sequence and these epigenetic changes are influenced by age and environmental factors, with DNA methylation being one of the best characterized epigenetic mechanisms. The human genome is predominantly methylated on CpG motifs, which results in gene silencing; however methylation within the body of the gene may mark active transcription. There is evidence suggesting an involvement of environmental factors in the pathogenesis of Alzheimer's disease (AD), which prompted our study examining DNA methylation in this disorder.
  
  
  METHODS
  Using immunohistochemistry with 5-methylcytosine/5-hydroxymethylcytosine antibodies we studied, in comparison with age matched controls, DNA methylation in sporadic and familial AD cases in the entorhinal cortex that exhibits substantial pathology and the cerebellum, which is relatively spared.
  
  
  RESULTS
  Neuronal nuclear labelling with 5-methylcytosine (5mC) and 5-hydroxymethylcytosine (5hmC) was evident in all cases studied. We did not detect any significant change in the levels of nuclear staining in the AD samples compared to neurologically normal controls. In the entorhinal cortex we also examined global DNA methylation and hydroxymethylation using an enzyme-linked immunosorbent assay (ELISA).
  
  
  CONCLUSIONS
  No significant differences were found between AD and control cases in global levels of 5mC and 5hmC in the entorhinal cortex using immunohistochemistry and enzyme-linked immunosorbent assays.
authors.affiliation: Queen Square Brain Bank for Neurological Disorders, Department of Molecular Neuroscience, UCL Institute of Neurology, London, UK.
authors.forename: Tammaryn
authors.initials: T
authors.lastname: Lashley
authors.affiliation: Queen Square Brain Bank for Neurological Disorders, Department of Molecular Neuroscience, UCL Institute of Neurology, London, UK.
authors.forename: Priya
authors.initials: P
authors.lastname: Gami
authors.affiliation: Queen Square Brain Bank for Neurological Disorders, Department of Molecular Neuroscience, UCL Institute of Neurology, London, UK.
authors.forename: Navid
authors.initials: N
authors.lastname: Valizadeh
authors.affiliation: Reta Lila Weston Research Laboratories and Department of Molecular Neuroscience, UCL Institute of Neurology, London, UK.
authors.forename: Abi
authors.initials: A
authors.lastname: Li
authors.affiliation: Queen Square Brain Bank for Neurological Disorders, Department of Molecular Neuroscience, UCL Institute of Neurology, London, UK.
authors.forename: Tamas
authors.initials: T
authors.lastname: Revesz
authors.affiliation: Queen Square Brain Bank for Neurological Disorders, Department of Molecular Neuroscience, UCL Institute of Neurology, London, UK.
authors.forename: Robert
authors.initials: R
authors.lastname: Balazs
mesh_terms: D044503:5-Methylcytosine / Q000378:metabolism / Q000031:analogs & derivatives; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000544:Alzheimer Disease / Q000235:genetics*; D003596:Cytosine / Q000031:analogs & derivatives / Q000378:metabolism; D019175:DNA Methylation; D018728:Entorhinal Cortex / Q000378:metabolism; D044127:Epigenesis, Genetic; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged
chemical_list: C011865:5-hydroxymethylcytosine; D044503:5-Methylcytosine; D003596:Cytosine
keywords: Alzheimer's disease; epigenetics; hydroxymethylation; methylation