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bioRxiv · 10.64898/2026.01.26.701799

Spatial transcriptomics reveals brain-wide circadian disruption in an Alzheimer's disease model

Gelber, A.·Romero, H.·Burrows, D.·Whittaker, D. S.·Carlin, D.·Mukamel, E. A.·Desplats, P.
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Abstract

Diurnal rhythms in brain transcription align neural, immune, and metabolic processes with the light-dark cycle and are profoundly disrupted in Alzheimers 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 Alzheimers disease pathogenesis.

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Gelber, A., Romero, H., Burrows, D., Whittaker, D. S., Carlin, D., Mukamel, E. A., Desplats, P.. 2026-01-28. Spatial transcriptomics reveals brain-wide circadian disruption in an Alzheimer's disease model. https://doi.org/10.64898/2026.01.26.701799

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