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Updated: Oct 1, 2025
Isolation of Cortical Microglia with Preserved Immunophenotype and Functionality From Murine Neonates
Published on: January 30, 2014
Transcriptional response of murine microglia in Alzheimer's disease and inflammation
Daniel C Shippy1, Jyoti J Watters2, Tyler K Ulland3
1Department of Pathology and Laboratory Medicine, University of Wisconsin, Madison, WI, USA.
Background:
Alzheimer's disease (AD) is a neurodegenerative disorder and is the most common cause of late-onset dementia. Microglia, the primary innate immune cells of the central nervous system (CNS), have a complex role in AD neuropathology. In the initial stages of AD, microglia play a role in limiting pathology by removing amyloid-β (Aβ) by phagocytosis. In contrast, microglia also release pro-inflammatory cytokines and chemokines to promote neuroinflammation and exacerbate AD neuropathology. Therefore, investigating microglial gene networks could identify new targets for therapeutic strategies for AD.
Results:
We identified 465 differentially expressed genes (DEG) in 5XFAD versus wild-type mice by microarray, 354 DEG in lipopolysaccharide (LPS)-stimulated N9 microglia versus unstimulated control cells using RNA-sequencing (RNA-seq), with 32 DEG common between both datasets. Analyses of the 32 common DEG uncovered numerous molecular functions and pathways involved in Aβ phagocytosis and neuroinflammation associated with AD. Furthermore, multiplex ELISA confirmed the induction of several cytokines and chemokines in LPS-stimulated microglia.
Conclusions:
In summary, AD triggered multiple signaling pathways that regulate numerous genes in microglia, contributing to Aβ phagocytosis and neuroinflammation. Overall, these data identified several regulatory factors and biomarkers in microglia that could be useful in further understanding AD neuropathology.
Insights
Microglia gene networks in Alzheimer's disease (AD) were analyzed. Key pathways regulating amyloid-beta (Aβ) clearance and neuroinflammation were identified, offering potential therapeutic targets for AD.
Area of Science:
- Neuroscience
- Immunology
- Genetics
Background:
- Alzheimer's disease (AD) is a leading cause of dementia, characterized by neurodegeneration.
- Microglia, the brain's immune cells, have a dual role in AD, clearing amyloid-beta (Aβ) but also promoting neuroinflammation.
- Understanding microglial gene networks is crucial for identifying new therapeutic strategies for AD.
Purpose of the Study:
- To investigate microglial gene expression patterns in Alzheimer's disease.
- To identify common differentially expressed genes (DEG) between AD models and stimulated microglia.
- To uncover molecular functions and pathways involved in AD neuropathology.
Main Methods:
- Gene expression profiling using microarray in 5XFAD versus wild-type mice.
- RNA sequencing (RNA-seq) of lipopolysaccharide (LPS)-stimulated N9 microglia compared to controls.
- Multiplex ELISA to confirm cytokine and chemokine induction.
Main Results:
- Identified 465 differentially expressed genes (DEG) in 5XFAD mice and 354 DEG in LPS-stimulated microglia.
- Found 32 common DEG between both datasets, highlighting shared molecular mechanisms.
- Confirmed induction of cytokines and chemokines in stimulated microglia, implicating neuroinflammation.
Conclusions:
- Alzheimer's disease activates microglial signaling pathways that regulate genes involved in Aβ phagocytosis and neuroinflammation.
- Identified regulatory factors and biomarkers in microglia that advance understanding of AD neuropathology.
- These findings suggest potential microglial targets for novel AD therapeutics.
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