Table I.
Reference | Methodology | Approach | Samples | N | Primary Findings |
---|---|---|---|---|---|
(Rao et al., 2012) | Real-Time PCR (MSRE-digested DNA) | Nine candidate genes previously identified as differentially expressed in AD | Human frontal cortex (BA9) | 10 AD 10 CTL |
Hypomethylation of inflammatory genes NF-ƙβ and COX-2 and hypermethylation of neuronal genes BDNF and synaptophysin in AD |
(Mastroeni et al., 2009) | Immunofluorescence | Global methylation (in monozygotic twin-pair discordant for AD) | Human temporal neocortex and cerebellum | 1 AD 1 CTL |
Global hypomethylation in neuronal nuclei in neocortex in AD |
(Mastroeni et al., 2010) | Immunofluorescence | Global methylation in AD and elderly control samples | Human temporal cortex and cerebellum | 20 AD 20 CTL |
Global hypomethylation in neuronal nuclei in entorhinal cortex in AD |
(Chouliaras et al., 2013) | Immunofluorescence | Global and cell-specific methylation and hydroxymethyation in AD and elderly control samples as well as monzygotic twin-pair discordant for AD | Human hippocampus (CA1, CA3 and DG) | 10 AD 10 CTL 1 AD 1 CTL |
Global decrease in 5mC and 5hmC in both glia and neurons in AD compared to control. |
(Bakulski et al., 2012) | Illumina Infinium Human Methylation 27K BeadArrays | Genome-wide analysis of >27,000 CpG sites | Human prefrontal cortex | 12 AD 12 CTL |
918 differentially methylated genes. The highest ranking gene (TMEM59) was confirmed by RT-PCR in an additional 13 AD and 13 CTL samples |
(Wang et al., 2008) | Sequenom Epityper (MALDI-TOF mass spectrometry) | Twelve Candidate genes associated with AD | Human prefrontal cortex | 24 AD 10 CTL |
Greater age-specific epigenetic drift from "normal" in AD |
(Siegmund et al., 2007) | Real-Time PCR (Bisulfite-treated DNA) | Fifty candidate genes related to CNS growth and development | Human temporal neocortex | 18 AD 63 CTL |
Hypomethylation of S100A2 and hypermethylation of SORBS3 in AD |
(West et al., 1995) | Southern Blot | One candidate gene previously associated with AD | Human frontal cortex (BA38) | 1 AD 1 PD 1 CTL |
Hypomethylation of APP gene in AD |
(Furuya et al., 2012) | Sequenom Epityper (MALDI-TOF mass spectrometry) | Correlation of mRNA and promoter methylation of synaptic protein SNAP25 | Human entorhinal cortex, auditory cortex and hippocampus | 10 AD 10 CTL |
No DNA methylation changes in SNAP25 promoter |
(Zhang et al., 2012) | Targeted proteomics, LC-MS/MS-TMT quantitative proteomics and Western Blotting | Comparison of histone acetylation levels using three methods | Human temporal lobe | 11 AD 4 CTL |
Decreased acetylation of Histone H3 in AD |
(Ogawa et al., 2003) | Immunohistochemistry | Comparison of Histone H3 phosphorylation in AD | Human hippocampus | 17 AD 9 CTL |
Increased phosphorylation of Histone H3 in neurons (cytoplasmic) in AD |
(Graff et al., 2012) | Immunohistochemistry | Comparison of HDAC1, 2 and 3 levels in CA1 field | Human hippocampus | 19 AD 7 CTL |
Increased levels of HDAC2 in CA1 neurons in AD |
Abbreviations: Methylation-sensitive restriction enzymes (MRSE), Brodmann area (BA), Alzheimer’s disease (AD), Control (CTL), Pick’s disease (PD), Nuclear factor kappa-light-chain-enhancer of activated B cells (NF-ƙβ), Cyclooxygenase-2 (COX-2), Transmembrane protein 59 (TMEM59), Real-time polymerase chain reaction (RT-PCR), S100 calcium binding protein A2 (S100A2), Sorbin and SH3 domain containing 3 (SORBS3), Amyloid precursor protein (APP), Synaptosomal-associated protein 25 (SNAP25), Liquid chromatography-mass spectrometry (LC-MS), Mass spectrometry-tandem mass tags (MS-TMT), Histone deacetylase (HDAC)