Related Experiment Video
Updated: Sep 12, 2025
Obtaining Human Microglia from Adult Human Brain Tissue
Published on: August 30, 2020
Alzheimer's disease transcriptional landscape in ex vivo human microglia
Roman Kosoy1,2,3,4, John F Fullard1,2,3,4, Jaroslav Bendl1,2,3,4
1Center for Disease Neurogenomics, Icahn School of Medicine at Mount Sinai, New York, NY, USA.
Abstract:
Microglia are resident immune cells of the brain and are implicated in the etiology of Alzheimer's disease (AD) and other diseases. Yet the cellular and molecular processes regulating their function throughout the course of the disease are poorly understood. Here, we present a transcriptional analysis of primary microglia from 189 human postmortem brains, including 58 healthy aging individuals and 131 with a range of disease phenotypes, such as 63 patients representing the full clinical and pathological spectra of AD. We identified changes associated with multiple AD phenotypes, capturing the severity of dementia and neuropathological lesions. Transcript-level analyses identified additional genes with heterogeneous isoform usage and AD phenotypes. We identified changes in gene-gene coordination in AD, dysregulation of coexpression modules and disease subtypes with distinct gene expression patterns. Taken together, these data further our understanding of the key role that microglia have in AD biology and nominate candidates for therapeutic intervention.
Insights
Microglia, the brain's immune cells, show altered gene expression in Alzheimer's disease (AD). This study reveals key molecular changes in microglia, offering potential therapeutic targets for AD.
Area of Science:
- Neuroimmunology
- Neuroscience
- Genomics
Background:
- Microglia are crucial brain immune cells involved in Alzheimer's disease (AD) pathogenesis.
- The precise molecular mechanisms governing microglial function in AD remain largely unknown.
Purpose of the Study:
- To conduct a comprehensive transcriptional analysis of microglia from human brains across a spectrum of aging and AD phenotypes.
- To identify molecular changes in microglia associated with AD severity and neuropathology.
Main Methods:
- Transcriptional analysis of primary microglia from 189 human postmortem brains (58 healthy aging, 131 with AD).
- Analysis included assessment of gene expression, isoform usage, gene-gene coordination, and coexpression modules.
Main Results:
- Identified significant microglial gene expression changes linked to multiple AD phenotypes and dementia severity.
- Discovered altered gene-gene coordination and dysregulated coexpression modules in AD brains.
- Revealed distinct gene expression patterns defining specific AD subtypes.
Conclusions:
- Microglia play a pivotal role in AD biology, with significant transcriptional alterations observed.
- The study nominates specific genes and molecular pathways for potential therapeutic intervention in AD.
