bioRxiv : the preprint server for biologyFeb 9, 2026

Brain-wide daily rhythm disruption in an Alzheimer's disease model revealed by gene mapping

Circadian Biology Weekly Brief ↗PubMed ↗DOI ↗

Updated Jun 27, 2026

Abstract

Essence

Spatial transcriptomics linked Alzheimer's-model pathology to early, region-specific disruption of brain diurnal transcription.

Evidence

This was a large-scale spatial transcriptomics study mapping 24-hour rhythmic transcription across cortical and subcortical regions in mouse brain and the APP23 Alzheimer's disease model.

Caveat

The work is in a mouse model and measures transcriptional rhythms before substantial amyloid plaque deposition, not human Alzheimer's disease progression.

Simplified

Diurnal rhythms in brain transcription align neural, immune, and metabolic processes with the light-dark cycle and are profoundly disrupted in Alzheimer's disease (AD). However, the regional organization of diurnal transcription in the healthy and diseased brain remains poorly defined. Using large-scale spatial transcriptomics, we mapped 24-hour rhythmic transcription across cortical and subcortical regions of the mouse brain. We identified marked regional differences in rhythmicity, including distinct oscillatory signatures across cortical areas and along the rostro-caudal axis. In the APP23 mouse model of AD, pathology-vulnerable brain regions exhibited early, region-specific disruption of diurnal transcription prior to substantial amyloid plaque deposition. These findings reveal a spatially organized architecture of brain diurnal rhythms and identify early rhythmic dysregulation as a feature of Alzheimer's disease pathogenesis.