Researchers created a detailed transcriptomic atlas of six brain regions, revealing cell-type-specific and region-specific vulnerabilities in Alzheimer's disease and highlighting astrocyte genes linked to cognitive resilience.
By Tarun Sai LomteReviewed by Susha Cheriyedath, M.Sc.Jul 25 2024 In a recent study published in the journal Nature, researchers presented a transcriptomic atlas of multiple brain regions in individuals with and without Alzheimer’s disease .
Study: Single-cell multiregion dissection of Alzheimer’s disease. Image Credit: Marko Aliaksandr / Shutterstock a, snRNA-seq profiling summary, covering 283 samples across 6 brain regions from 48 participants from ROSMAP, showing global pathology, Braak stage and pathological or clinical diagnosis of AD and 32 no dementia). b,c, Joint uniform manifold approximation and projection , colored by major cell type and region of origin . d, The regional composition of major cell types. e, Relative enrichment of major cell types across regions by quasi-binomial regression.
Thalamic astrocytes were enriched for focal adhesion-related genes, while cortical astrocytes were enriched for those involved in glutamate processing and transport. Next, the team explored how AD impacts cellular composition. There were slight decreases in excitatory and inhibitory neurons and increased oligodendrocytes and vascular cells, driven by differences in PFC, EC, and HC regions, particularly in late AD.
Further, the researchers computed differentially expressed genes for each excitatory subtype. Non-vulnerable subtype-linked DEGs were enriched for diverse functions, including heat-shock family chaperones, ubiquitin-ligase binding, and neuronal death mediators. By contrast, vulnerable subtype-linked DEGs were only enriched for mitochondrial oxidative phosphorylation.
Brain Cell Astrocyte Cortex Dementia Gene Gene Expression Genes Hippocampus Intracellular Microglia Neocortex Neuron Neurons Pathology Proteoglycan Ribonucleic Acid RNA Signaling Pathway Thalamus Vascular
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