Ogg1 regulates context-dependent glial states in Alzheimer's disease

Ogg1 deficiency impairs memory and alters glial transcription in physiological conditions, but in APP/PS1 mice it improves memory, lowers amyloid burden, and reduces AD-linked glial remodeling.

• Why it matters: Oxidative DNA damage is an early AD hallmark, yet whether Ogg1, a DNA repair enzyme, shapes AD pathogenesis and glial states is unclear.
• What they did: The study compared Ogg1-deficient versus sufficient mice under physiological versus APP/PS1 disease conditions, assessing memory, amyloid burden, glial remodeling, and transcriptional/chromatin changes, including single-nucleus transcriptomics.
• The result: Ogg1 effects were context-dependent without changing global 8-oxo-dG levels, and Ogg1-dependent glial transcriptional programs were strongly conserved in human AD, suggesting a non-canonical role in transcriptional regulation.

AI summary of the abstract · may contain errors · not medical advice · read the paper.