Single-cell and single-nuclei RNA sequencing as powerful tools to decipher cellular heterogeneity and dysregulation in neurodegenerative diseases

Frontiers in Cell and Developmental Biology 2022

Cuevas-Diaz Duran, Raquel and Gonz{\'a}lez-Orozco, Juan Carlos and Velasco, Iv{\'a}n and Wu, Jia Qian

Abstract

Alzheimer’s disease (AD) is a neurodegenerative disorder marked by cognitive decline, primarily affecting memory and executive function. This review highlights recent advancements in single-cell sequencing and spatial transcriptomics, which provide detailed insights into the cellular heterogeneity and neuroimmune mechanisms of AD. The review addresses the need for understanding complex cellular interactions to identify novel therapeutic targets and biomarkers. Single-cell sequencing has revolutionized our understanding by mapping gene expression at the individual cell level, revealing distinct microglial and astrocytic states that contribute to neuroinflammation and neurodegeneration. These technologies have uncovered disease-associated microglial subpopulations and gene expression changes linked to AD risk genes, essential for developing targeted therapies. In conclusion, the integration of single-cell and spatial transcriptomics with other omics data is crucial for a comprehensive understanding of AD, paving the way for personalized medicine. Continued interdisciplinary collaboration will be vital in translating these findings into effective treatments, improving patient outcomes.

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