Single Cell Atlas Shows Links In Cognitive Function Dementia Alzheimer Resilience

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Summary

In the quest to unravel the complexities of Alzheimer's disease, researchers have crafted a detailed transcriptomic map of the aged human prefrontal cortex, examining over two million cells from brains of 427 individuals with varying Alzheimer's pathology. This groundbreaking study illuminated common changes in certain neuron types linked to Alzheimer's, highlighted a simultaneous rise in DNA repair and cohesin complex components in key brain cells, and pinpointed specific genes and pathways tied to cognitive health and Alzheimer's resilience. Significantly, it shed light on the vulnerability of specific inhibitory neurons in Alzheimer's, while also revealing neuron groups associated with maintained cognitive function in later life, offering insights into the intricate relationship between these neurons and Alzheimer's resistance.

Fig.1 Graphical abstract¹.

Research Criteria

In their research, the team created a comprehensive atlas of the elderly human prefrontal cortex at the single-cell level, analyzing 2.3 million cells from 427 deceased individuals' brains. These participants exhibited different levels of Alzheimer's disease pathology and cognitive decline. The objective was to uncover the cellular and molecular factors associated with cognitive ability, dementia, and resistance to Alzheimer's disease-related changes.

Fig.2 Experimental design¹.

Sample Type

Prefrontal cortex of brain tissue

Result—A Transcriptional Atlas of The Aged Human Prefrontal Cortex With 23 Million Nuclei

The study meticulously analyzed over 2.3 million nuclei from the prefrontal cortex of 427 individuals, using single-nucleus RNA-sequencing. This diverse cohort, drawn from the Religious Order Study and the Rush Memory and Aging Project, spanned various stages of Alzheimer's disease (AD), from non-AD to advanced stages. Participants were categorized based on their cognitive status at death, including those with no cognitive impairment, mild cognitive impairment, and AD dementia. After refining the data to remove low-quality cells, the research identified 54 distinct cell types within 12 major groups, encompassing a range of neuron subtypes, oligodendrocytes, astrocytes, immune cells like microglia, and several vascular cell types. This detailed cellular mapping enhances our understanding of the aged human prefrontal cortex and its relation to AD progression, representing a significant step forward in brain aging and disease research.

Fig.3 Single-nucleus RNA-seq analysis of prefrontal cortex samples from 427 ROSMAP study contributors¹.

Result—Systematic Differential Analysis of Gene Expression

In this study, researchers analyzed gene expression across 54 cell types in relation to Alzheimer's Disease (AD) pathology and other factors like diabetes and lifestyle variables. They found that AD pathology significantly influenced gene expression in nearly all cell types, especially in the context of neurotic plaques and neurofibrillary tangles. A unique pattern was observed in oligodendrocytes with diabetes. Additionally, sex-specific responses to AD pathology were noted. The study revealed a substantial overlap in gene expression changes across various neuron subtypes and other cells, such as astrocytes. These findings, validated through comparisons with previous studies and different datasets, highlight the complex genetic interplay in AD, offering crucial insights into its molecular mechanisms.

Fig.4 Changes in gene expression related with Alzheimer's disease pathogenesis are found in all excitatory neuron subtypes¹.

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Single Nuclei RNA Sequencing Service

At Creative Biolabs, we pride ourselves on offering custom-tailored, top-quality single nuclei RNA sequencing service, aimed at advancing biomedical research worldwide. Our expertly designed platform is ideal for detailed study of complex tissues such as the brain, heart, kidney, and even unique cryopreserved samples. Our state-of-the-art approach is instrumental in enhancing the understanding of tumor cell diversity and uncovering the intricacies of various disease processes.

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At Creative Biolabs, we specialize in delivering exceptional single nuclei RNA sequencing services, tailored for the biomedical research community. Our expertise lies in dissecting gene expression at the individual nucleus level, shedding light on cell diversity and operations. Leveraging advanced methodologies and tools, we guarantee top-notch outcomes, handling a spectrum of samples, from intricate tissues to unique, frozen specimens. Committed to excellence, our proficient team ensures swift and effective support, enhancing your scientific research journey.

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Reference

1. Mathys, Hansruedi, et al. "Single-cell atlas reveals correlates of high cognitive function, dementia, and resilience to Alzheimer's disease pathology." Cell 186.20 (2023): 4365-4385.