Epigenomic Aberrations in Brains of Humans with Mild Cognitive Impairment and Alzheimer’s Disease [re-analysis]

During the progression of neurodegenerative disorders, epigenomic aberrations may contribute to gene dysregulation, leading to manifestation of symptoms. To test this, we employed a multifaceted approach to investigate how the two key histone methylation marks, H3K4me3 (linked to gene activation) and H3K27me3 (linked to gene suppression), are altered in postmortem prefrontal cortex of humans with Mild Cognitive Impairment (MCI) or Alzheimer’s Disease (AD).

Compared to controls, MCI and AD exhibited pronounced losses of permissive H3K4me3 peaks at promoters of genes enriched in synaptic plasticity and neurotransmission, and significant gains of H3K4me3 peaks at promoters of genes enriched in transcriptional regulation. AD displayed more substantial H3K4me3 losses on synaptic genes than MCI. Conversely, significant gains of repressive H3K27me3 peaks were observed at synaptic gene promoters in both disease groups, with MCI exhibiting more pronounced H3K27me3 gains on synaptic genes than AD.