Cell-type specific daily rhythms in the human brain linked to Alzheimer's disease, daily stress, and protein-making disruptions

Core clock rhythms are preserved in Alzheimer's disease, but cell-type-specific circadian outputs are disrupted.

• Circadian expression profiles were reconstructed from post-mortem cortical samples of 409 individuals with and without Alzheimer's disease.
• Many cell types exhibited disrupted rhythms in ribosomal biogenesis and oxidative phosphorylation despite preserved core clock rhythms.
• Losses in ribosomal gene expression rhythms were observed in both Alzheimer's patients and APP/PS1 mice.
• APP/PS1 mice demonstrated further reductions in ribosomal protein expression and translation following circadian desynchrony.
• Exploratory computational modeling suggests that altered translation may contribute to increased circadian variability in Alzheimer's patients.

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