AI Article Synopsis

  • - The study investigates the complex causes of Alzheimer's disease (AD) by using advanced techniques to analyze genetic information from both sporadic AD and Down Syndrome-related AD (DSAD). - Researchers found specific changes in gene expression linked to where pathology accumulates in the brain's cortical layers, highlighting inflammation in upper layers as significant in AD. - The study also compared findings from human samples to data from an amyloid model in mice to better understand how amyloid-related changes affect gene expression across different species.

Article Abstract

The pathogenesis of Alzheimer's disease (AD) depends on environmental and heritable factors, with its molecular etiology still unclear. Here we present a spatial transcriptomic (ST) and single-nucleus transcriptomic survey of late-onset sporadic AD and AD in Down syndrome (DSAD). Studying DSAD provides an opportunity to enhance our understanding of the AD transcriptome, potentially bridging the gap between genetic mouse models and sporadic AD. We identified transcriptomic changes that may underlie cortical layer-preferential pathology accumulation. Spatial co-expression network analyses revealed transient and regionally restricted disease processes, including a glial inflammatory program dysregulated in upper cortical layers and implicated in AD genetic risk and amyloid-associated processes. Cell-cell communication analysis further contextualized this gene program in dysregulated signaling networks. Finally, we generated ST data from an amyloid AD mouse model to identify cross-species amyloid-proximal transcriptomic changes with conformational context.

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Source
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC11631771PMC
http://dx.doi.org/10.1038/s41588-024-01961-xDOI Listing

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