Single-cell transcriptomic analysis of Alzheimer’s disease
By H. Mathys, J. Dávila-Velderrain, Zhuyu Peng, Fan Gao, S. Mohammadi, J. Z. Young, M. Menon, Liang He, Fatema Abdurrob, Xueqiao Jiang and 6 more. Nature, 2019
2,170 citations recorded by the source corpus.
Alzheimer’s disease is a pervasive neurodegenerative disorder, the molecular complexity of which remains poorly understood. Here, we analysed 80,660 single-nucleus transcriptomes from the prefrontal cortex of 48 individuals with varying degrees of Alzheimer’s disease pathology. Across six major brain cell types, we identified transcriptionally distinct subpopulations, including those associated with pathology and characterized by regulators of myelination, inflammation, and neuron survival. The strongest disease-associated changes appeared early in pathological progression and were highly cell-type specific, whereas genes upregulated at late stages were common across cell types and primarily involved in the global stress response. Notably, we found that female cells were overrepresented in disease-associated subpopulations, and that transcriptional responses were substantially different between sexes in several cell types, including oligodendrocytes. Overall, myelination-related processes were recurrently perturbed in multiple cell types, suggesting that myelination has a key role in Alzheimer’s disease pathophysiology. Our single-cell transcriptomic resource provides a blueprint for interrogating the molecular and cellular basis of Alzheimer’s disease. Single-cell transcriptomics from 48 individuals with varying degrees of Alzheimer’s disease pathology demonstrates that gene-expression changes in Alzheimer’s disease are both cell-type specific and shared, and that transcriptional responses show sexual dimorphism.
View Paper: https://www.semanticscholar.org/paper/2a3f8208aadb36d1c90d869252fa5f052bace572
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Citations in the corpus
- Role of neuroinflammation in neurodegeneration development (2023, background): “In normal human brains, APOE is mainly derived from astrocytes,(35,163) while its expression by microglia is induced by ageing as well as amyloid and tau pathology.(35,164,165) There are three isoforms of APOE gene in humans, respectively, APOE2, APOE3, APOE4.”
- Human Monocyte Subsets and Phenotypes in Major Chronic Inflammatory Diseases (2019, result): “Interestingly, transcriptional changes in response to the earlier disease stages were more cell type-specific in comparison with more ubiquitous late stage variations where the genes being upregulated represented a more general stress response (156).”
- Transcriptome-scale spatial gene expression in the human dorsolateral prefrontal cortex (2020, methodology): “We further assessed the robustness of this approach by re-analyzing processed snRNA-seq from 48 donors across 70,634 nuclei obtained from the human prefrontal cortex (BA10) across 44 broad clusters in a study of Alzheimer’s disease (Mathys et al., 2019).”
- Alzheimer Disease: An Update on Pathobiology and Treatment Strategies (2019, unknown): “Single nuclear transcriptomic techniques have recently been applied to human AD brain specimens and have identified microglial subtypes with increased Apoe expression but have failed to identify DAM or MGnD subpopulations similar to what has been seen in the mouse brain (Mathys et al., 2019).”