Reconstructed cell-type-specific rhythms in human brain link Alzheimer's pathology, circadian stress, and ribosomal disruption.

ABSTRACT: Alzheimer's disease (AD) disrupts behavioral circadian rhythms, but its effects on molecular rhythms in the human brain are poorly understood. Using single-nucleus RNA sequencing (snRNA-seq) from post-mortem cortical samples, we informatically estimated the relative circadian phases of 409 persons with and without AD dementia, reconstructing circadian expression profiles across cell types. Although core clock rhythms were preserved in AD, many cell-type-specific circadian outputs were disrupted. Rhythms in ribosomal biogenesis and oxidative phosphorylation were dampened across cell types. Similar losses in ribosomal gene expression rhythms were observed in amyloid precursor protein/presenilin 1 (APP/PS1) mice, which showed further reductions in ribosomal protein expression and polysome-med

SUBMITTER: Hollis HC 

PROVIDER: S-EPMC12352436 | biostudies-literature | 2025 Sep

REPOSITORIES: biostudies-literature