Related Experiment Video
Updated: Jul 6, 2025
09:12
Isolation of Cortical Microglia with Preserved Immunophenotype and Functionality From Murine Neonates
Published on: January 30, 2014
15.9K
iPSC-derived PSEN2 (N141I) astrocytes and microglia exhibit a primed inflammatory phenotype
Michael A Sullivan1, Samuel D Lane1, André D J McKenzie1
1School of Medical Sciences, The Faculty of Medicine and Health, The University of Sydney, Camperdown, Australia.
Journal of Neuroinflammation
|January 4, 2024
Summary
This study differentiated Alzheimer's disease (AD) astrocytes and microglia from PSEN2 (N141I) mutation patients. These cells showed altered morphology, inflammation, and amyloid-beta processing, indicating a primed AD phenotype.
Area of Science:
- Neuroscience
- Genetics
- Cell Biology
Background:
- Glia and immune pathways are implicated in Alzheimer's disease (AD) progression.
- Induced pluripotent stem cell (iPSC)-derived glial cells from AD patients exhibit diverse disease-related phenotypes.
- Previous studies were limited to specific AD mutations (PSEN1, APOE, APP) or sporadic cases.
Purpose of the Study:
- To differentiate and characterize iPSC-derived microglia and astrocytes from patients with the PSEN2 (N141I) mutation.
- To investigate the inflammatory and morphological profiles of these PSEN2 (N141I)-mutant glial cells.
Main Methods:
- Generated iPSC-derived astrocytes and microglia-like cells from healthy controls and familial AD patients with a PSEN2 (N141I) mutation.
- Characterized cell identity and morphology using immunofluorescent microscopy.
- Assessed inflammatory responses via cytokine/chemokine release (ELISAs, multi-cytokine arrays) after LPS and Aβ42 stimulation, and measured phagocytic capacity for Aβ42.
Main Results:
- AD-derived astrocytes and microglia showed reduced morphological complexity compared to controls.
- PSEN2 (N141I)-mutant astrocytes exhibited increased GFAP/S100β, enhanced Aβ42 phagocytosis and secretion.
- AD-derived glial cells displayed exaggerated pro-inflammatory cytokine secretion (IL-6, CXCL1, ICAM-1, IL-8, IL-18, MIF) upon immune challenge.
Conclusions:
- Successfully differentiated and characterized iPSC-derived astrocytes and microglia-like cells from PSEN2 (N141I) mutation carriers.
- PSEN2 (N141I)-mutant glial cells displayed a 'primed' phenotype.
- This phenotype includes reduced complexity, heightened pro-inflammatory responses, and altered Aβ42 handling, offering insights into AD pathogenesis.
