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Published on: June 1, 2016
Association between APOE genotype and microglial cell morphology
Courtney M Kloske1, Mary D Gearon2, Erica M Weekman1
1Department of Physiology, College of Medicine, Sanders-Brown Center on Aging, University of Kentucky, Lexington, Kentucky, USA.
Abstract:
APOE is the largest genetic risk factor for late-onset Alzheimer disease (AD) with E4 conferring an increased risk for AD compared to E3. The ApoE protein can impact diverse pathways in the brain including neuroinflammation but the precise impact of ApoE isoforms on inflammation remains unknown. As microglia are a primary source of neuroinflammation, this study determined whether ApoE isoforms have an impact on microglial morphology and activation using immunohistochemistry and digital analyses. Analysis of ionized calcium-binding adaptor molecule 1 (Iba1) immunoreactivity indicated greater microglial activation in both the hippocampus and superior and middle temporal gyrus (SMTG) in dementia participants versus non-demented controls. Further, only an increase in activation was seen in E3-Dementia participants in the entire SMTG, whereas in the grey matter of the SMTG, only a diagnosis of dementia impacted activation. Specific microglial morphologies showed a reduction in ramified microglia in the dementia group. For rod microglia, a reduction was seen in E4-Control patients in the hippocampus whereas in the SMTG an increase was seen in E4-Dementia patients. These findings suggest an association between ApoE isoforms and microglial morphologies and highlight the importance of considering ApoE isoforms in studies of AD pathology.
Insights
Apolipoprotein E (ApoE) isoforms influence Alzheimer's disease (AD) risk. This study found ApoE isoforms impact microglial activation and morphology, suggesting their importance in AD neuroinflammation.
Area of Science:
- Neuroscience
- Genetics
- Immunology
Background:
- Apolipoprotein E (ApoE) is a major genetic risk factor for late-onset Alzheimer's disease (AD).
- The E4 isoform (ApoE4) increases AD risk compared to the E3 isoform (ApoE3).
- ApoE's role in brain neuroinflammation, particularly its impact on microglia, is not fully understood.
Purpose of the Study:
- To investigate the impact of different Apolipoprotein E (ApoE) isoforms on microglial morphology and activation.
- To determine if ApoE isoforms influence neuroinflammatory responses in Alzheimer's disease (AD).
Main Methods:
- Immunohistochemistry was used to analyze microglial markers.
- Digital image analysis quantified microglial morphology and activation states.
- Ionized calcium-binding adaptor molecule 1 (Iba1) immunoreactivity was assessed in brain regions of AD participants and controls.
Main Results:
- Microglial activation was elevated in dementia participants compared to controls in the hippocampus and superior and middle temporal gyrus (SMTG).
- Specific microglial morphologies, such as ramified microglia, were reduced in the dementia group.
- ApoE isoforms were associated with distinct changes in microglial morphology, with rod microglia showing differential distribution in E4 carriers.
Conclusions:
- Apolipoprotein E (ApoE) isoforms are associated with altered microglial activation and morphology in Alzheimer's disease (AD).
- These findings underscore the significance of considering ApoE isoforms in understanding AD neuropathology and neuroinflammation.
- Microglial responses vary depending on both dementia status and ApoE genotype.
