Spatial transcriptomics identifies regional disruptions in brain rhythmic gene expression in a mouse model of Alzheimer’s disease

In addition to cognitive decline, behavioral disturbances in the sleep-wake cycle such as progressive fragmentation of sleep, decreased total sleep time, and increased confusion or restlessness in the evening (sundowning) are a hallmark of AD. Emerging evidence suggests that these disruptions in sleep and behavior may be underpinned by molecular dysregulation of the circadian clock.

Here, we utilize Visium spatial transcriptomics to characterize diurnal transcriptional rhythms across various brain regions in APP23 transgenic mice, a model of AD, and their non-transgenic littermates in 7- and 14-month old mice. We reveal significant alterations in rhythmic gene expression in APP23-TG mice, particularly in the hippocampus and cortex. These changes were evident in 7-month-old animals, coinciding with early amyloid deposition and persisted with advancing pathology.