Ogg1 regulates context-dependent glial states in Alzheimer's disease
- 1Norwegian University of Science and Technology
Abstract
Oxidative DNA damage is an early hallmark of Alzheimer's disease (AD), but whether Ogg1, a key enzyme in oxidative DNA repair, contributes to disease pathogenesis remains unclear. Here, we show that Ogg1 exerts opposing effects under physiological and disease conditions. Ogg1 deficiency impaired memory and induced glial transcriptional alterations under physiological conditions, whereas in APP/PS1 mice it improved memory, reduced amyloid burden and attenuated AD-associated glial remodeling. These effects occurred without changes in global 8-oxo-dG levels and were accompanied by changes in chromatin accessibility and gene expression, supporting a non-canonical role for Ogg1 in transcriptional regulation. Single-nucleus transcriptomics revealed strong transcriptional responses to Ogg1 deficiency across all major glial cell types and showed that Ogg1-dependent glial transcriptional programs are strongly conserved in human AD. These findings identify Ogg1 as a context-dependent regulator of glial cell states and reveal an unexpected role in AD-associated glial remodeling.
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BibTeX
@misc{abentung2026ogg1,
title = {{Ogg1 regulates context-dependent glial states in Alzheimer's disease}},
author = {A. Abentung and T. Sakshaug and P. Schnur and M. Egiazarian and C. Damiao and K. Aakre and T. Obermann and M. Sousa and N. Kunath and M. Bjoras and K. Scheffler},
howpublished = {bioRxiv},
year = {2026},
month = nov,
doi = {10.64898/2026.11.06.764857},
url = {https://www.biorxiv.org/content/10.64898/2026.11.06.764857v1},
note = {CC BY},
}
RIS
TY - UNPB
TI - Ogg1 regulates context-dependent glial states in Alzheimer's disease
AU - A. Abentung
AU - T. Sakshaug
AU - P. Schnur
AU - M. Egiazarian
AU - C. Damiao
AU - K. Aakre
AU - T. Obermann
AU - M. Sousa
AU - N. Kunath
AU - M. Bjoras
AU - K. Scheffler
PY - 2026
DA - 2026/11/06
PB - bioRxiv
DO - 10.64898/2026.11.06.764857
UR - https://www.biorxiv.org/content/10.64898/2026.11.06.764857v1
AB - Oxidative DNA damage is an early hallmark of Alzheimer's disease (AD), but whether Ogg1, a key enzyme in oxidative DNA repair, contributes to disease pathogenesis remains unclear. Here, we show that Ogg1 exerts opposing effects under physiological and disease conditions. Ogg1 deficiency impaired memory and induced glial transcriptional alterations under physiological conditions, whereas in APP/PS1 mice it improved memory, reduced amyloid burden and attenuated AD-associated glial remodeling. These effects occurred without changes in global 8-oxo-dG levels and were accompanied by changes in chromatin accessibility and gene expression, supporting a non-canonical role for Ogg1 in transcriptional regulation. Single-nucleus transcriptomics revealed strong transcriptional responses to Ogg1 deficiency across all major glial cell types and showed that Ogg1-dependent glial transcriptional programs are strongly conserved in human AD. These findings identify Ogg1 as a context-dependent regulator of glial cell states and reveal an unexpected role in AD-associated glial remodeling.
ER -