Cross-region reduction in 5-hydroxymethylcytosine in Alzheimer's disease brain

TY - JOUR

T1 - Cross-region reduction in 5-hydroxymethylcytosine in Alzheimer's disease brain

AU - Condliffe, Daniel

AU - Wong, Andrew

AU - Troakes, Claire

AU - Proitsi, Petroula

AU - Patel, Yogen

AU - Chouliaras, Leonidas

AU - Fernandes, Cathy

AU - Cooper, Jonathan

AU - Lovestone, Simon

AU - Schalkwyk, Leonard

AU - Mill, Jonathan

AU - Lunnon, Katie

PY - 2014/8

Y1 - 2014/8

N2 - 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.

AB - 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.

KW - Epigenetics

KW - DNA methylation

KW - Brain

KW - 5-methylcytosine

KW - 5-mC

KW - 5-hydroxymethylcytosine

KW - 5-hmC

KW - 5-formylcytosine

KW - 5-fC

KW - 5-carboxylcytosine

KW - 5-caC

KW - Alzheimer's disease

KW - EMBRYONIC STEM-CELLS

KW - DNA METHYLATION

KW - FRONTAL-CORTEX

KW - 5-METHYLCYTOSINE

KW - GENOME

KW - 5-FORMYLCYTOSINE

KW - HYDROXYMETHYLATION

KW - REPLICATION

KW - GENES

KW - ROLES

U2 - 10.1016/j.neurobiolaging.2014.02.002

DO - 10.1016/j.neurobiolaging.2014.02.002

M3 - Article

SN - 0197-4580

VL - 35

SP - 1850

EP - 1854

JO - Neurobiology of Aging

JF - Neurobiology of Aging

IS - 8

ER -