University Of Tasmania

File(s) under permanent embargo

id #12216 - Dysregulation of the neuronal epigenome occurs prior to pathology-onset and alters with progressive amyloidosis

conference contribution
posted on 2023-05-24, 20:24 authored by Andrew PhippsAndrew Phipps, Giles, K, Mercer, T, James VickersJames Vickers, Robinson, M, Phillippa TaberlayPhillippa Taberlay, Adele WoodhouseAdele Woodhouse
Epigenetic machinery is at the interface between our genes and the environment and is well placed to explain some of the heritability gap of sporadic Alzheimer’s disease (AD). The dysfunction and death of neurons underlie the symptoms of AD, yet few studies focus on neuronal epigenetic alterations in AD. We examined H3K4me3 and H3K27ac histone modifications (ChIP-seq) in neurons from 3, 6 and 12-month-old wild-type and APP/PS1 mice, representing pre-pathology, pathology-onset and pathology-rich time-points (n=5/genotype/timepoint). H3K27ac and H3K4me3 marking at promoters was increased in APP/PS1 versus wild-type neurons at the pre-pathology time-point. Enhancers and superenhancers were also differentially enriched for H3K27ac marking between APP/PS1 and wild-type neurons at both pre-pathology and pathology-onset time-points. Interestingly, promoters and enhancers followed a similar pattern of enrichment for H3K4me3 and H3K27ac across the time-course of amyloidosis, whereas super-enhancers exhibited a different pattern of H3K27ac enrichment over time. We observed a partial recapitulation of a pre-pathology/juvenile-like histone landscape in both aged wild-type and APP/PS1 neurons (>23% of differentially H3K4me3 and H3K27ac marked sites were shared). To validate our findings, we compared our data to human neuronal single-cell RNA-seq data (Mathys et al., 2019, Nature). Over 80% of the transcripts that were differentially expressed between neurons from human AD cases and controls exhibited differential promoter enrichment for H3K4me3 between wild-type and APP/PS1 neurons at the pathology-rich time-point. Our data provides a unique insight into the epigenetic dysregulation occurring in neurons in a milieu of amyloidosis.


The Mason Foundation



Wicking Dementia Research Education Centre


Australasian Neuroscience Society

Place of publication


Event title

Australasian Neuroscience Society (ANS) 2019 Conference

Event Venue

Adelaide Convention Centre

Date of Event (Start Date)


Date of Event (End Date)


Repository Status

  • Restricted

Socio-economic Objectives

Expanding knowledge in the biomedical and clinical sciences

Usage metrics

    University Of Tasmania