Table 7.
Epigenetic dysregulation in Alzheimer’s disease: chromatin remodeling.
| Chromatin Remodelling | Regulation | Epigenetic | Observed in | Sample | Methods | Reference |
|---|---|---|---|---|---|---|
| Target | modification | size | ||||
| Histones (Globally) | ↓ | Acetylation | AD patients | 5–6 | Targeted Proteomics assay |
Zhang et al., 2012 |
| H3 | ↑ | Acetylation (BACEl promoter region) |
AD patients | 31 | FAlRE/ChIP | Marques et al., 2012 |
| Acetylation | AD mouse model (3xTg-AD mice; 4 months of age) |
6 | IF | Walker et al., 2013 | ||
| AD mouse model (Tg2576 mice; PFC) |
N.S. | N.S. | Lithner et al., 2009 | |||
| ↑ | Phosphorylation | AD mouse model (Tg2576 mice; PFC) | ||||
| ↓ | AD patients (Hippocampus) | |||||
| ↑ | Methylation | AD mouse model (Tg2576 mice; PFC) |
||||
| ↓ | Methylation | AD mouse model (Tg2576 mice; Striatum) | ||||
| H3K9 | ↑ | Tri-methylation | AD monozygotic twin (temporal cortex and hippocampus) |
l | IHC | Ryu et al., 2008 |
| H4 | ↓ | Acetylation | AD mouse model (APP/PS1) | 4 | WB | Francis et al., 2009 |
| ↑ | Acetylation | AD mouse model (3xTg-AD mice; 4 months of age) |
6 | IF | Walker et al., 2013 | |
| ↑ | Acetylation | AD mouse model (Tg2576 mice; CA1) |
N.S. | N.S. | Lithner et al., 2009 | |
| H2AX (S1S9) | ↑ | Phoshorylation | AD patients (Hippocampus and Astrocytes) |
13 | ICC | Myung et al., 2008 |
| HDAC2 | ↑ | Expression | AD mouse models (CK-p25, 5xFAD, Cdk5cKO mice; Hippocampus and PFC) AD patients (Hippocampus and EC) |
6–9 4–8 |
IHC, WB, Co-IP, ChIP, PCR |
Graff et al., 2012 |
| H2BKS | ↓ | Acetylation | AD mouse models (CK-p25, 5xFAD, Cdk5cKO mice; Hippocampus and PFC) |
6–9 | ||
| HSKl4 | ↓ | Acetylation | AD mouse models (CK-p25, | 6–9 | ||
| H4KS | ↓ | Acetylation | 5xFAD, Cdk5cKO mice; Hippocampus and PFC) |
|||
| H4Kl2 | ↓ | Acetylation | Mice (16 month old) | 4–5 | ChIP, PCR, HAT/HDAC assay |
Peleg et al., 2010 |
| SlRTl | ↓ | Expression | AD patients (parietal cortex) | l9 | WB, ISH | Julien et al., 2009 |
| ↑ | Expression | AD mouse model (3xTg-AD mice) |
N.S. | |||
indicates increased expression levels,
indicates decreased expression levels, and
indicates altered expression, not further specified.
Abbreviations: 3xTg-AD mice, triple transgenic mouse model of AD; 5xFAD, transgenic mouse model overexpressing mutant human APP (695) with the Swedish (K670N and M671L), Florida (I716V), and London (V717I) mutations, and mutant human presenilin 1 with the M146L and L286V familial AD mutations; AD, Alzheimer’s disease; BACE1, β-secretase 1; CA, cornu ammonis; Cdk5 KO mice; cyclin-dependent kinase 5 knock-out mouse model; CK-p25 mice, transgenic mouse model overexpressing p25 under control of an inducible calcium/ calmodulin-dependent protein kinase II α promoter; EC, entorhinal cortex; H, histone; HDAC, histone deacetylase; K, lysine; PFC, prefrontal cortex; S, serine; SIRT, sirtuin; Tg2576 mice, transgenic mice overexpressing human APP isoform 695 with the double KM670/671NL Swedish mutation; N.S., not specified; FAIRE, formaldehyde-assisted isolation of regulation; IF: immunofluorescence; ICC, immunocytochemistry; Co-IP, protein complex immunoprecipitation; IHC, immunohistochemistry; ChIP, chromatin immunoprecipitation; PCR, polymerase chain reaction; WB, Western blot; ISH: in situ hybridization.