The detailed characteristics of neuronal cell populations in Alzheimer’s disease (AD) using single-cell RNA sequencing have not been fully elucidated. To explore the characterization of neuronal cell populations in AD, this study utilized the publicly available single-nucleus RNA-sequencing datasets in the transgenic model of 5X familial Alzheimer’s disease (5XFAD) and wild-type mice to reveal an AD-associated excitatory neuron population (C3:Ex.Neuron). The relative abundance of C3:Ex.Neuron increased at 1.5 months and peaked at 4.7 months in AD mice. Functional pathways analyses showed that the pathways positively related to neurodegenerative disease progression were downregulated in the C3:Ex.Neuron at 1.5 months in AD mice. Based on the differentially expressed genes among the C3:Ex.Neuron, four subtypes (C3.1–4) were identified, which exhibited distinct abundance regulatory patterns during the development of AD. Among these subtypes, the C3.1 neurons [marked by netrin G1 (Ntng1)] exhibited a similar regulatory pattern as the C3:Ex.Neuron in abundance during the development of AD. In addition, our gene set variation analysis (GSEA) showed that the C3.1 neurons, instead of other subtypes of the C3:Ex.Neuron, possessed downregulated AD pathways at an early stage (1.5 months) of AD mice. Collectively, our results identified a previously unidentified subset of excitatory neurons and provide a potential application of these neurons to modulate the disease susceptibility.
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Dr. David Lowemann, M.Sc, Ph.D., is a co-founder of the Institute for the Future of Human Potential, where he leads the charge in pioneering Self-Enhancement Science for the Success of Society. With a keen interest in exploring the untapped potential of the human mind, Dr. Lowemann has dedicated his career to pushing the boundaries of human capabilities and understanding.
Armed with a Master of Science degree and a Ph.D. in his field, Dr. Lowemann has consistently been at the forefront of research and innovation, delving into ways to optimize human performance, cognition, and overall well-being. His work at the Institute revolves around a profound commitment to harnessing cutting-edge science and technology to help individuals lead more fulfilling and intelligent lives.
Dr. Lowemann’s influence extends to the educational platform BetterSmarter.me, where he shares his insights, findings, and personal development strategies with a broader audience. His ongoing mission is shaping the way we perceive and leverage the vast capacities of the human mind, offering invaluable contributions to society’s overall success and collective well-being.