Basic Science and Pathogenesis

Area of Science:

• Neuroscience
• Endocrinology
• Cell Biology

Background:

• Amyloid pathology, common in Alzheimer's disease (AD) and type 2 diabetes (T2D), impacts cellular environments.
• T2D is a frequent comorbidity of AD, suggesting shared pathophysiological processes.

Purpose of the Study:

• To compare cellular and transcriptomic responses to amyloid pathology in the AD brain and T2D pancreas.
• To identify shared molecular pathways between AD and T2D.

Main Methods:

• Xenium single-cell spatial transcriptomics on human post-mortem AD brain and T2D pancreas tissues.
• Integration of transcriptomic data with amyloid histopathology to assess cell proximity.
• Analysis of cell type composition and differential gene expression relative to amyloid deposits.

Main Results:

• Increased microglia near brain amyloid; increased macrophages and activated stellate cells near pancreatic amyloid.
• Differential gene expression observed in astrocytes, microglia, oligodendrocytes, endothelial cells (brain), and acinar, alpha, activated stellate cells (pancreas).
• 16 shared differentially expressed genes identified across both organs, including CAV1, CXCR4, MS4A6A, SNCG, and SOX2.

Conclusions:

• Spatial analysis reveals amyloid deposits alter cellular and transcriptomic microenvironments in both brain and pancreas.
• Identification of shared genes differentially expressed near amyloid deposits suggests common pathological mechanisms in AD and T2D.