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Profiling Microglia From Alzheimer's Disease Donors and Non-demented Elderly in Acute Human Postmortem Cortical
Astrid M Alsema1, Qiong Jiang1, Laura Kracht1
1Department of Biomedical Sciences of Cells and Systems, Section Molecular Neurobiology, University of Groningen, University Medical Center Groningen, Groningen, Netherlands.
Abstract:
Microglia are the tissue-resident macrophages of the central nervous system (CNS). Recent studies based on bulk and single-cell RNA sequencing in mice indicate high relevance of microglia with respect to risk genes and neuro-inflammation in Alzheimer's disease (AD). Here, we investigated microglia transcriptomes at bulk and single-cell levels in non-demented elderly and AD donors using acute human postmortem cortical brain samples. We identified seven human microglial subpopulations with heterogeneity in gene expression. Notably, gene expression profiles and subcluster composition of microglia did not differ between AD donors and non-demented elderly in bulk RNA sequencing nor in single-cell sequencing.
Insights
Microglia, the brain's immune cells, show diverse subtypes in humans. Alzheimer's disease (AD) did not alter microglial gene expression or subpopulation composition in postmortem brain samples.
Area of Science:
- Neuroscience
- Immunology
- Genomics
Background:
- Microglia are key immune cells in the central nervous system (CNS).
- Microglia are implicated in neuroinflammation and Alzheimer's disease (AD) pathogenesis.
- Previous studies in mice suggest microglial involvement in AD risk genes.
Purpose of the Study:
- To investigate microglial transcriptomic profiles in human brain samples from AD patients and non-demented controls.
- To identify and characterize distinct human microglial subpopulations.
- To determine if AD affects microglial gene expression or subpopulation composition.
Main Methods:
- Bulk and single-cell RNA sequencing of human postmortem cortical brain samples.
- Analysis of transcriptomes from microglia of non-demented elderly individuals and AD donors.
- Identification and characterization of microglial subpopulations based on gene expression.
Main Results:
- Seven distinct human microglial subpopulations were identified, exhibiting heterogeneity in gene expression.
- No significant differences were observed in overall microglial gene expression profiles between AD and non-demented donors.
- The composition of microglial subclusters remained consistent between AD and control groups.
Conclusions:
- Human microglia display significant transcriptomic heterogeneity with distinct subpopulations.
- Contrary to some mouse studies, bulk and single-cell transcriptomic analyses did not reveal differences in microglia between AD and non-demented elderly individuals.
- These findings suggest that major alterations in microglial gene expression or composition may not be a primary feature in the investigated human AD cortical samples.
