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Application of single-cell sequencing technology and its clinical implications in Parkinson’s disease and Alzheimer’s disease: a narrative review

Zhong Chen,Jack Shi,Longfei Li

Published 2025 in Advanced Technology in Neuroscience

ABSTRACT

Genetic materials, including DNA and RNA molecules in the nucleus and cytosol, contain vital information related to protein production, metabolic regulation, and signal transduction. Understanding these molecules and their expression levels is important for research in different fields of biology, especially in the study of human disease. Owing to the development of next-generation sequencing technology, single-cell sequencing technology measures gene expression levels from mRNAs through the process of reverse transcription, allowing researchers to gain insights into the overexpression/low expression of specific proteins in various cells in particular disease models, which could help researchers explore the signaling pathways associated with the cellular and molecular mechanisms of these diseases. For example, single-cell sequencing has revealed the selective vulnerability of dopamine neurons and nuclear factor κB signaling pathway pathways associated with the progression of Parkinson’s disease. In Alzheimer’s disease research, single-cell sequencing has helped identify subpopulations of cells associated with disease pathology and has provided insights into the inflammatory response associated with the disease. Herein, we review the application of single-cell sequencing technology and its clinical implications in Parkinson’s disease and Alzheimer’s disease. As life expectancy increases annually, the incidence of neurodegenerative diseases is on the rise. This trend underscores the urgency and relevance of the use of single-cell sequencing to explore the anomalous expression levels of pathogenic genes and related signaling pathways in different brain regions. This paper introduces three subtypes of total RNA sequencing, namely, single-nucleus sequencing, single-cell sequencing, and spatial sequencing. It also introduces several advanced applications of these technologies in the research of Parkinson’s disease and Alzheimer’s disease. At the same time, this paper also explores the challenges contained in these sequencing methods and discusses their possible developments in the future. Overall, single-cell sequencing technology provides new tools and methods for Parkinson’s disease and Alzheimer’s disease research. Despite these challenges, there is great potential to improve our understanding of these complex diseases and to develop new therapies.

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