Table 1 Summary of classical HPTMs in AD

Acetylation

Human brain

H3K9ac

H3K9ac is related to tau-related pathology and chromatin remodeling

[81]

Human brain

H3K9ac, H3K27ac, H3K122ac

1. H3K9ac and H3K27ac increase and H3K122ac reduction in AD

2. H3K9ac and H3K27ac are related to transcription, chromatin, and disease pathways

[20]

Human brain

H3K27ac

H3K27ac is associated with transcriptional variation at proximal genes

[19]

Human brain

H4K16ac

H4K16ac reduction in AD

[21]

Mice

H4K5ac, H4K12ac

App specifically regulates H4K5ac and H4K12ac and affects early memory-related genes in memory

[82]

Mice

H4 acetylation

4-PBA treatment enhances the expression of genes related to induced learning and memory genes by increasing neuronal H4 acetylation

[83]

Human brain

H3 acetylation, H4 acetylation

H3 acetylation and H4 acetylation increase in high-pathological areas, with no significant change observed in low-pathological areas

[84]

Mice

H4 acetylation

APP/PS1 mice display a reduced H4 acetylation levels in response to a learning task

[85]

Mice

H3K9ac, H4K12ac

ACSS2 downregulation mediates a reduction in glutamate receptor expression through histone acetylation, which exacerbates synaptic plasticity impairment in AD

[22]

IPSC cell lines

H3K27ac

Knocking down P300/CBP reduces H3K27ac, inhibits the expression of genetic programs compensating for increased Aβ load, and leads to increased Aβ secretion

[23]

Drosophila

H4 acetylation

H4 acetylation may act as a defense against AD pathology-related insults

[25, 26]

Methylation

Human brain, Mice

H3K9me2

Repressive H3K9me2 and euchromatic histone methyltransferases EHMT1 and EHMT2 are significantly elevated in the PFC

[31]

Human brain, Mice

H3K4me3

H3K4me3 and its catalytic enzymes are significantly elevated in the PFC in AD

[30]

Human brain

H4K20me2,

H3K4me2,

H3K27me3,

H3K79me1,

H3K79me2,

H3K36me2,

H4K20me3,

H3K27me1,

H3K56me1

H4K20me2, H3K4me2, H3K27me3, and H3K79me1 increased, while H3K79me2, H3K36me2, H4K20me3, H3K27me1, and H3K56me1 decreased in AD

[20]

Mice

H3K4me3

Histone methylation is actively regulated in the hippocampus and facilitates long-term memory formation

[28]

Mice

H3K4me2,

H3K4me3

KMT2B mediates hippocampal H3K4me2 and H3K4me3, which is critical for memory formation

[27]

Mice

H3K9me2

Increased H3K9me2 levels in the cerebral cortex region and hippocampus region

[86]

Mice

H3K9me2

NEP is significantly reduced in AD, and hypoxia may downregulate NEP by increasing H3K9me2

[32]

Mice

H3K4me

A decrease in H3K4 methylation, resulting from KMT2A knockdown, partially recapitulates the pattern previously reported in CK-p25 mice

[29]

Human brain

H2BK108me,

H4R55me

Reduced H2BK108 and H4R55 methylation in the frontal cortex region

[39]

Phosphorylation

Human brain

H4S47p

H4S47p increases in AD

[35]

Human brain

H2AXS139p (γH2AX)

In the hippocampus region and cerebral cortex region, γH2AX significantly increased

[38]

Human brain

H3S10p

Activated H3S10p in AD is restricted to the neuronal cytoplasm

[36]

Human brain

H3 phosphorylation

H3 phosphorylation increases in AD

[37]

Ubiquitination

Human brain

H2BK120ub

H2BK120ub increases in the frontal cortex of AD

[39]

Human neurons

H2A ubiquitination

Bmi1/Ring1 protein complex maintains the transcriptional inhibition of developmental genes through H2Aub

[41]

Mice

H2B ubiquitination

A deficiency of H2Bubi in the hippocampus prevents learning-induced increases in H3K4me3, gene transcription, synaptic plasticity, and memory formation

[40]